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A set of orthogonal states in multipartite systems is called to be locally stable if to preserve the orthogonality of the states, only trivial local measurement can be performed for each partite. Locally stable sets of states are always locally indistinguishable yielding a form of nonlocality which is different from the Bell-type nonlocality. In this work, we study the locally stable set of product states with small size. First, we give a lower bound on the size of locally stable sets of product states. It is well known that unextendible product basis (UPB) is locally indistinguishable. But we find that some of them are not locally stable. On the other hand, there exists some small subsets of minimum size UPB that are also locally stable which implies the nonlocality of such UPBs are stronger than other form. [ABSTRACT FROM AUTHOR]

This study delves into measurement strategies within a scenario where multiple pairs of Alices and Bobs independently and sequentially observe entangled states. The goal is to maximize the number of observer pairs (A k , B l) capable of witnessing entanglement. Previous research has shown that arbitrary pairs (A k , B k) (k ≤ n) can detect entanglement in all pure entangled states and a specific class of mixed entangled states [ Pandit et al. (2022) [37] ]. However, it's worth noting that other pairs (A k , B l) with (k ≠ l ≤ n) may not observe entanglement using the same method. Additionally, a novel strategy is introduced, allowing every pair of arbitrarily many Alices and Bobs to witness entanglement regardless of whether the initial state is a Bell state or a particular class of mixed entangled states. These findings contribute to our understanding of measurement strategies aimed at maximizing entanglement observation in various contexts. [ABSTRACT FROM AUTHOR]

Guanidine acetic acid is a naturally occurring amino acid derivative that acts as a direct precursor of creatine, an important compound in muscle and nerve tissue energy metabolism. Guanidine acetic acid, as a new nutritional additive, has no obvious side effects on animals, which plays an important role in improving animal growth performance and carcass quality. The paper reviews the basic metabolic pathway of guanidine acetic acid biotransformation and its application in animal production, to provide reference for the application of guanidine acetic acid in livestock and poultry breeding industry. [ABSTRACT FROM AUTHOR]

Recently, Halder et al (2019 Phys. Rev. Lett. 122 040403) proposed the concept of strong nonlocality without entanglement: an orthogonal set of fully product states in multipartite quantum systems that is locally irreducible for every bipartition of its subsystems. Due to the complexity of the problem, most results are limited to tripartite systems. Here we consider a weaker form of nonlocality which is called local distinguishability based genuine nonlocality. A set of orthogonal multipartite quantum states is said to be genuinely nonlocal if it is locally indistinguishable for every bipartition of the subsystems. In this work, we study how to construct sets of orthogonal product states which are genuinely nonlocal. Firstly, we present a set of product states with simple structure in bipartite systems that is locally indistinguishable. After that, based on a simple observation, we present a general method to construct genuinely nonlocal sets of multipartite product states by using those sets that are genuinely nonlocal but with less parties. As a consequence, we obtain that genuinely nonlocal sets of fully product states exist in any L parties systems ⨂ i = 1 L C d i provided L ⩾ 3 and d i ⩾ 3 for all i. [ABSTRACT FROM AUTHOR]

Recently, Doroudiani and Karimipour [Phys. Rev. A 102 012427(2020)] proposed the notation of planar maximally entangled states which are a wider class of multipartite entangled states than absolutely maximally entangled states. There they presented their constructions in the multipartite systems but the number of particles is restricted to be even. Here, we first solve the remaining cases, i.e., constructions of planar maximally entangled states on systems with odd number of particles. In addition, we generalized the PME to the planar k-uniform states whose reductions to any adjacent k parties along a circle of N parties are maximally mixed. We presented a method to construct sets of planar k-uniform states which have minimal support. [ABSTRACT FROM AUTHOR]

Purpose. To investigate the outcome of pars plana vitrectomy (PPV) with suitable internal limiting membrane peeling (ILM) and air tamponade for patients with highly myopic foveoschisis-associated lamellar macular hole (MH). Methods. This retrospective interventional case series included 11 patients with highly myopic foveoschisis-associated lamellar MH who underwent PPV and indocyanine green-aided ILM peeling up to the temporal vascular arcades. Following air tamponade after surgery, all patients were instructed to maintain a face-down position. The patients were followed up for over 1 year and evaluated for MH closure and the best-corrected visual acuity before and after surgery. Results. The mean ± standard deviation values of patient age, axial length, and follow-up duration were 67.82 ± 6.54 years, 29.21 ± 1.95 mm, and 24.27 ± 8.11 months, respectively. After surgery, the lamellar MH closed in all eyes, and 10 eyes showed vision improvement at the 1-month, 3-month, and final follow-up evaluations. One patient showed decreased vision at 2 years after surgery, with patchy chorioretinal atrophy in the macular region. Myopic foveoschisis showed resolution in three eyes and alleviation in eight. Ten patients underwent cataract surgery during PPV. Conclusion. Extension of ILM peeling up to the temporal vascular arcades and air tamponade after PPV may improve the visual function and rate of MH closure for patients with highly myopic foveoschisis-associated lamellar MH. [ABSTRACT FROM AUTHOR]

Graphical abstract Non-fullerene acceptors (s4, s5, and s6) exhibiting high light-absorbing capacities and electron mobility were designed for OSCs. Highlights • Three novel small molecule acceptors (s4, s5, and s6) were reported. • The properties of s1-s6 and PffBT4T-2OD/s1-s6 were calculated by theoretical methods. • s4, s5, and s6 exhibit greater exciton separation ability and electron mobility. Abstract Acceptor-π-donor-π-acceptor (A-π-D-π-A) type small molecule acceptors have made significant progress in organic solar cells (OSCs). To achieve high performance acceptors, three novel acceptors (s4-s6) are designed and investigated based on small molecule acceptors (s1-s3) via introduction of different end-capped groups. The quantum chemistry and Marcus theory approaches are used to calculate the electronic structures and crucial parameters dramatically related to the short-circuit current density (J SC), involving the absorption spectrum, electron-hole correlation, driving force, and electron mobility. Compared with s1-s3, s4-s6 not only yield greater red-shift and stronger and broader absorption spectra, but also exhibit much higher electron mobility, easier exciton dissociation abilities, and much better electron transfer efficiencies in active layer. Our results will offer theoretical guidelines for further design and synthesis of acceptors to enhance the performance of OSCs. [ABSTRACT FROM AUTHOR]

The genetic diversity and population structure of oriental thin-skinned melons, Cucumis melo subsp. agrestis , remain incompletely clear to date. In the present study, 163 melon accessions (153 subsp. agrestis and 10 subsp. melo accessions) mainly from India and China were examined for genetic diversity and population structure using a core set of 37 simple sequence repeat (SSR) markers evenly distributed across the 12 melon chromosomes. A total of 274 alleles were detected with the allelic number per marker ranging from 3 to 16 (mean = 7.40) and polymorphism information content (PIC) from 0.342 to 0.770 (mean = 0.524). With the SSR genotype data, two main groups (I and II), mainly represented by Indian and Chinese subsp. agrestis accessions, respectively, were obtained by the unweighted pair group method with arithmetic mean (UPGMA) and the principal component analysis (PCA). Group I contained 24 Indian subsp. agrestis landraces and four accessions from America and Maldives while group II was consisted of 122 Chinese accessions and 13 accessions from other seven countries. There existed a clear divergence between Indian and Chinese subsp. agrestis melons, resulting in two independent germplasm pools. Group II mainly represented by East Asian accessions could be further divided into three subgroups (II-1, II-2, and II-3). The analysis of molecular variance (AMOVA) and pairwise F statistics ( F ST ) were performed to quantify the genetic differentiation among the whole panel, displaying a strong differentiation between Indian and Chinese subsp. agrestis accessions but a comparatively weak differentiation within East Asian pool. From these findings, Indian and Chinese subsp. agrestis accessions have a distant relationship with each other and probably undergo different domestication pathways in their domestication history. Our results provide useful information for pursuing the genetic diversity and structure of oriental thin-skinned melon resources, which will favour efficient utilization of these valuable germplasms in modern agriculture and breeding. [ABSTRACT FROM AUTHOR]

We study the perfectly local indistinguishability of multipartite product states. Firstly, we follow the method of Zhang et al. (Phys Rev A 93:012314, 2016) to give another more concise set of $$2n-1$$ orthogonal product states in $${\mathbb {C}}^m\otimes {\mathbb {C}}^n$$ $$(4\le m\le n)$$ which can not be distinguished by local operations and classical communication. Then we use the three-dimensional cubes to present some product states which give us an intuitive view on how to construct locally indistinguishable product states in tripartite quantum systems. At last, we give an explicit construction of locally indistinguishable orthogonal product states for general multipartite systems. [ABSTRACT FROM AUTHOR]

Recently, trace distance measure of coherence has been proposed for characterizing the coherence of a given quantum state. However, it seems difficult to estimate the optimal incoherent state for high dimensional states. An explicit expression for the trace distance measure of coherence for a class of qudit states is provided. We show that the closest incoherent state to the class of qudit states is just the diagonal matrix obtained from it by deleting all off-diagonal elements. It is also shown that the measure of coherence induced by trace distance can act as a measure of coherence for this class of qudit states with some restrictions on the strictly incoherent operations. [ABSTRACT FROM AUTHOR]

In this paper, we study the one-way local operations and classical communication (LOCC) problem. In $$\mathbb {C}^d\otimes \mathbb {C}^d$$ with $$d\ge 4$$ , we construct a set of $$3\lceil \sqrt{d}\rceil -1$$ one-way LOCC indistinguishable maximally entangled states which are generalized Bell states. Moreover, we show that there are four maximally entangled states which cannot be perfectly distinguished by one-way LOCC measurements for any dimension $$d\ge 4$$ . [ABSTRACT FROM AUTHOR]

Phosphorus (P) solubility and transformation in soils determine its availability to plants and loss potential to the environment, and soil P dynamics is impacted by fertilization and soil properties. A Ultisol sample was interacted with 20 mg L−1P solution from one to ten times. The P-reacted soils were then analyzed for water-soluble P (0.01 M calcium chloride (CaCl2)–extractable P); plant-available P (Olsen P); ammonium chloride P, aluminum P, iron P (NH4Cl-P, Al-P, Fe-P, respectively); and occluded P (Oc-P). The degree of P saturation (DPS) was calculated from ammonium oxalate–extractable Al, Fe, and P. The amount of P sorbed by the soil was highly correlated with the frequency of P addition with high percentage of P adsorbed initially and gradually decreased as the P addition continued. The relative abundance of the five P fractions in the P-reacted soil was in the order of Fe-P (36.5 percent) > Al-P (35.6 percent) > Oc-P (22.8 percent) > Ca-P (2.7 percent) > NH4Cl-P (2.3 percent). Both Olsen P and CaCl2-P were significantly increased by the repeated P addition process and highly correlated in an exponential function. The DPS was increased above the so-called critical point of 25 percent after the first P saturation process and kept increasing as the P addition continued. The P availability and adsorption in the soil were controlled by soil free and amorphous Al and Fe. The results suggest that repeated P application will build soil P to an excessive level, and consequently result in poor P-use efficiency and high P-loss potential to surface and groundwater. [ABSTRACT FROM PUBLISHER]

Background: Diabetic retinopathy is severe damage to the retina caused by complications of diabetes, and is the prevailing cause of blindness. Accumulating evidence from both animal models and humans suggests that the inflammatory process plays a key role in the development of diabetic retinopathy and is facilitated by innate immune response. The aim of this study was to examine whether the TLR4 signaling pathway was involved in the streptozotocin-induced diabetic rat retina. Methods: Diabetes was induced by a single intraperitoneal injection of streptozotocin, and rat diabetic retinopathy was examined at 4 weeks of diabetes duration. Then the accumulated leukocytes were counted in vivo by acridine orange leukocyte fluorography, and the retinal vascular permeability was measured by the Evans blue assay. The expressions of TLR4 and its downstream signaling molecules were measured by RT-PCR or Western blot respectively. To evaluate the effect of blocking TLR4 on diabetic retinopathy, TAK-242, a selective TLR4 antagonist, was administered by intraperitoneal injection. Results: Our results showed that the retina of diabetic rats demonstrated accumulated leukocytes and retinal vascular permeability. The mRNA and protein expressions of TLR4 were upregulated in streptozotocin-treated diabetic rat retina. Furthermore, the protein levels of TLR4 downstream signaling molecules were significantly increased in streptozotocin-treated animals. In addition, the protein levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and interferon (IFN)-β, three downstream proinflammatory cytokines of TLR4 signal transduction pathway, were also markedly increased in diabetic rats. Administration of TAK-242 attenuated leukocytes accumulated and retinal vascular permeability, and decreased TLR4 downstream signaling molecules and proinflammatory cytokines in streptozotocin-induced animals. Conclusions: Together, these data have demonstrated that TLR4 has a critical role in streptozotocin-induced diabetic retinopathy at the level of inflammatory cytokine induction, in both the MyD88-dependent and MyD88-independent pathways. TLR4 may become a new potential pharmacological target for treating diabetic retinopathy. [ABSTRACT FROM AUTHOR]

In this paper, we give a method for the local unitary equivalent problem which is more efficient than that was proposed by Bin Liu et al []. [ABSTRACT FROM AUTHOR]

Background: Ocular blood flow provides a new perspective for studying the effects of diabetes and ischemic heart disease on systemic blood flow, pathological mechanisms, and prognosis. Previous studies have analyzed the hemodynamic changes of the ophthalmic artery (OA) in patients with diabetes and ischemic heart disease, but the results remain controversial due to limited observation methods. We aimed to explore the morphological and hemodynamic features in the OA in patients with type 2 diabetes (T2D) with and without acute coronary syndrome (ACS). Methods: In total, 134 participants, including 30 control participants, 34 with ACS only, 34 with T2D only, and 36 with both ACS and T2D, undergoing computed tomography angiography were enrolled. Three-dimensional OA models were reconstructed, and morphological parameters of the OA were measured. In addition, numerical simulations using computational fluid dynamics were used to acquire hemodynamic parameters of the OA. Results: In this study, 134 OA models were reconstructed. Morphological measurements revealed a smaller initial OA diameter in the T2D group than in the other two ACS groups. A hemodynamic simulation showed a significantly lower OA blood velocity in patients with ACS and T2D than that in controls (P < 0.001). The mass flow ratios in all disease groups were lower than those in the control group (P < 0.001, P = 0.020, and P < 0.001, respectively). The ACS and T2D groups had higher OA pressure levels than those of the control group (P = 0.013). The OA blood velocity and mass flow ratio were correlated with several clinical parameters. Conclusions: This study revealed morphological and hemodynamic differences in the OA between patients with T2D with and without ACS. Furthermore, the hemodynamic characteristics of the OA correlated with clinical prognostic biomarkers, suggesting the potential predictive ability of the OA. [ABSTRACT FROM AUTHOR]

Background: Ocular blood flow provides a new perspective for studying the effects of diabetes and ischemic heart disease on systemic blood flow, pathological mechanisms, and prognosis. Previous studies have analyzed the hemodynamic changes of the ophthalmic artery (OA) in patients with diabetes and ischemic heart disease, but the results remain controversial due to limited observation methods. We aimed to explore the morphological and hemodynamic features in the OA in patients with type 2 diabetes (T2D) with and without acute coronary syndrome (ACS).Methods: In total, 134 participants, including 30 control participants, 34 with ACS only, 34 with T2D only, and 36 with both ACS and T2D, undergoing computed tomography angiography were enrolled. Three-dimensional OA models were reconstructed, and morphological parameters of the OA were measured. In addition, numerical simulations using computational fluid dynamics were used to acquire hemodynamic parameters of the OA.Results: In this study, 134 OA models were reconstructed. Morphological measurements revealed a smaller initial OA diameter in the T2D group than in the other two ACS groups. A hemodynamic simulation showed a significantly lower OA blood velocity in patients with ACS and T2D than that in controls (P < 0.001). The mass flow ratios in all disease groups were lower than those in the control group (P < 0.001, P = 0.020, and P < 0.001, respectively). The ACS and T2D groups had higher OA pressure levels than those of the control group (P = 0.013). The OA blood velocity and mass flow ratio were correlated with several clinical parameters.Conclusions: This study revealed morphological and hemodynamic differences in the OA between patients with T2D with and without ACS. Furthermore, the hemodynamic characteristics of the OA correlated with clinical prognostic biomarkers, suggesting the potential predictive ability of the OA. [ABSTRACT FROM AUTHOR]

The present cross-sectional study was conducted to assess and compare the prevalence of dental caries of 229 deaf adolescents in a special senior high school and to identify factors related to dental caries, with a match group of 196 healthy adolescents in a normal senior high school, in Jiangsu province of East China. In this study the prevalence of dental caries was 55.9%, Decayed, Missing and Filled Teeth (DMFT) index in deaf students was 1.40±1.89; in healthy students was 13.8% and 1.36±1.72, respectively. Relatively lower proportion of awareness on dental health knowledge and lower proper practice of dental health behavior have been observed among deaf students compared with the control group. Multiple logistic regressions showed that the risk factors of dental caries in deaf students involved high frequency of consuming dessert and carbonated beverage. Poor oral health, lack of oral health knowledge and proper oral health practice could be found in deaf students. The dental treatment for the two groups was urgently needed. The dental health education concerning dietary behavior and prevention program to the deaf students and their parents should be reinforced; the supervision of oral health behavior for deaf and healthy students needs to be strengthened. [Copyright &y& Elsevier]

Abstract: Progesterone has been used in the hormonal treatment of endometrial cancer (EC) for many years, but the response rates are unsatisfying. The down-regulated progesterone receptor (PR) is the main reason for treatment failure. The insulin-like growth factor (IGF) system is related to EC risk, and IGF-I can inhibit PR transcription in breast cancer. Recent evidence suggests that metformin-combined oral contraceptives may reverse progesterone-resistant atypical endometrial hyperplasia, but the mechanism is unclear. We attempt to investigate the interaction of metformin, PR and IGF-II expression, and identify whether metformin can enhance the antitumor effect of medroxyprogesterone acetate (MPA) using Ishikawa and HEC-1B EC cell lines. We found that both IGF-I and IGF-II inhibit PR A/B mRNA and protein expression, whereas metformin markedly promotes PR expression. In parallel, IGF-II increases phosphorylation of AKT and p70S6K, while metformin increases AMPK phosphorylation and decreases p70S6K phosphorylation. The effects of metformin on PR A/B and p70S6K are partially reversed by an AMPK inhibitor. Furthermore, metformin synergistically antiproliferates MPA in two cell lines, with the peak synergy occurring with 10μM metformin combined with 1μM MPA (CI=0.20448 for Ishikawa, CI=0.12801 for HEC-1B). Our results demonstrate that metformin promotes PR expression, which can be inhibited by overexpressed IGF-II in EC. This effect is partially mediated through activating AMPK followed by inhibiting the overactivated mTOR pathway. [Copyright &y& Elsevier]

Abstract: The compositional dependence of glass-forming ability (GFA) was investigated for the Ti–Ni–Si ternary alloys. Glassy ribbons varied with different thicknesses were fabricated via single-roller melt spinning. The optimized glass-forming composition was located at Ti57Ni35Si8, with a critical thickness of about 200μm for complete glass formation. By characterizing the microstructure of arc-melted ingots of the Ti–Ni–Si ternary alloys, we demonstrate that the glass formation of the Ti57Ni35Si8 alloy correlates with the (L →Ti2Ni+TiNi+Ti5Si3) ternary eutectic reaction. In addition, the eutectic composition of the (L →Ti2Ni+TiNi+Ti5Si3) ternary and (L →TiNi+Ti5Si3) pseudo-binary eutectic reaction was determined to be in the vicinity of Ti63Ni31Si6 and Ti53Ni37Si10, with the invariant reaction temperature at 1243 and 1424K, respectively. [Copyright &y& Elsevier]

Abstract: In the present study, we investigated the mechanisms of apoptosis resistance and the roles of the phosphorylation of BRCA1, p21, the Bax/Bcl-2 protein ratio and cell cycle arrest in IR-induced apoptosis in MCF-7 cells. X-irradiation, in particular at low dose (1Gy), but not carbon ion irradiation, had a significant antiproliferative effect on the growth of MCF-7 cells. 1Gy X-irradiation resulted in G1 and G2 phase arrest, but 4Gy induced a significant G1 block. In contrast, carbon ion irradiation resulted in a significant accumulation in the G2 phase. Concomitant with the phosphorylation of H2AX induced by DNA damage, carbon ion irradiation resulted in an approximately 1.9–2.8-fold increase in the phosphorylation of BRCA1 on serine residue 1524, significantly greater than that detected for X-irradiation. Carbon ion irradiation caused a dramatic increase in p21 expression and drastic decrease in Bax expression compared with X-irradiation. The data implicated that phosphorylation of BRCA1 on serine residue 1524 might, at least partially, induce p21 expression but repress Bax expression. Together, our results suggested that the phosphorylation of BRCA1 at Ser-1524 might contribute to the G2 phase arrest and might be an upstream signal involved in preventing apoptosis signal via upregulation of p21 and downregulation of the Bax/Bcl-2 ratio. [Copyright &y& Elsevier]

No bulk metallic glass (BMG) has been observed so far in the Ti-Cu binary system. It has been found that by choosing a pseudo-binary eutectic (L → TiCu +TiNi) deeper than that in the binary, reachable via only small substitution of Cu with Ni, the glass-forming ability can be effectively elevated. BMGs of 1-1.5 mm diameter have been formed over a composition range around Ti50Cu43Ni7. The new BMGs are reproducibly malleable with significant compressive plastic strains. [ABSTRACT FROM AUTHOR]

A new copper complex of dmit, hexadecyltrimethylammonium bis(2-thioxo-1,3-dithiole-4,5-dithiolato)-copper([C16H33(CH3)3N][Cu(dmit)2], abbreviated as CTCU, C16H33(CH3)3N = hexadecyltrimethylammonium, dmit = 2-thioxo-1,3-dithiole-4,5-dithiolate) has been synthesized and its structure determined by X-ray diffraction. The saturable absorption of CTCU at 1053 nm shows promise as a Q-switch dye in the near IR regions. [ABSTRACT FROM AUTHOR]

Abstract: Two novel dmit2− salts: [C16H33(CH3)3N]Co(dmit)2 and [C16H33(CH3)3N]Ni(dmit)2 (abbreviated as CTCo and CTNi, respectively, and dmit2− =4,5-dithiolate-1,3-dithiole-2-thione), are synthesized and their third-order optical nonlinearities of the acetone solutions are investigated using Z-scan technique with 40ps pulse width at 1064nm. The Z-scan spectra reveal both CTCo and CTNi sample solutions possess large negative nonlinear refraction, exhibiting a self-defocusing effect. In addition, slight two-photo absorption and strong saturable absorption have been found in CTCo and CTNi, respectively. The molecular second-order hyperpolarizability γ eff of the CTNi molecule was estimated to be as high as (−4.6±0.2)×10−30 esu, which was four times larger than that of CTCo. An explanation for this enhancement is given. All the results suggest that these materials may have potential applications in the field of nonlinear optics. [Copyright &y& Elsevier]

Abstract: A completely randomized controlled study based on a rabbit model was designed to study the effect of repetitive ischemic preconditioning (IPC) on a spinal cord ischemic reperfusion injury. Twenty four white adult Japanese rabbits were randomly assigned to one of the 3 groups (n =8 per group): Group I: sham-operation group, Group II: ischemic reperfusion group, and, Group III: IPC group. Spinal cord ischemia was induced by infra-renal aortic cross-clamp for 45 min in Group II. Before 45 min ischemia, the rabbits in Group III underwent four cycles of IPC (5 min of ischemia followed by 5 min of reperfusion). Post-operative neurological function, electromyography (EMG) of rear limbs, and spinal cord histopathological changes were measured. The concentrations of calcium, magnesium, copper, and zinc in spinal cord were measured in the 7th day. The neurological function and histopathological changes in Group II were significantly different from those in Group I or Group III (P <0.05 or 0.01). There was a more significant change of EMG in Group II than that in Group III (P <0.05). The concentrations of calcium and copper in Group II were significantly higher (P <0.05 or 0.01), but magnesium and zinc were significantly lower (P <0.05) than those in Group I. Calcium and copper in Group II were significantly higher (P <0.05), but zinc was significantly lower (P <0.01) than those in Group III. In conclusion, repetitive IPC can protect rabbit spinal cord from ischemic reperfusion injury in a timely manner, which is associated with corrections of imbalance of calcium, magnesium, copper, and zinc in the ischemic region. [Copyright &y& Elsevier]

Electrochemical cleavage of DNA in the presence of copper–sulfosalicylic acid [Cu(ssal)22+] complex was studied. The cleavage was observed in a certain potential region where redox cycling of Cu(ssal)22+/Cu(ssal)2+ took place. Cu(ssal)22+ complex mediate generation of reactive oxygen species from O2 by the Fenton reaction, these radicals are capable of damaging DNA. The cleaved DNA fragments were separated by high-performance liquid chromatography (HPLC). The experimental results indicated that the method for electrochemical cleavage of DNA by Cu(ssal)22+ complex was simple and efficient. [Copyright &y& Elsevier]

Electrochemically induced DNA cleavage in the presence of copper-bipyridyl (Cu(bpy)22+) was studied at a gold electrode in a thin layer cell. The experiment results showed that DNA can be efficiently cleaved at −0.60 V (vs. Ag/AgCl) by this method. The extent of DNA cleavage increased as the working potential was shifted more negative in air-saturated solution. Electrolysis time and the concentration of Cu(bpy)22+ complex influenced the extent of DNA cleavage as well. The cleaved DNA fragments were separated by high performance liquid chromatography (HPLC). The results proved that this method of electrochemically induced DNA cleavage by Cu(bpy)22+ complex is simple, mild and highly efficient. [Copyright &y& Elsevier]

Maintaining placental endocrine homeostasis is crucial for a successful pregnancy. Pre‐eclampsia (PE), a gestational complication, is a leading cause of maternal and perinatal morbidity and mortality. Aberrant elevation of testosterone (T0) synthesis, reduced estradiol (E2), and melatonin productions have been identified in preeclamptic placentas. However, the precise contribution of disrupted homeostasis among these hormones to the occurrence of PE remains unknown. In this study, we established a strong correlation between suppressed melatonin production and decreased E2 as well as elevated T0 synthesis in PE placentas. Administration of the T0 analog testosterone propionate (TP; 2 mg/kg/day) to pregnant mice from E7.5 onwards resulted in PE‐like symptoms, along with elevated T0 production and reduced E2 and melatonin production. Notably, supplementation with melatonin (10 mg/kg/day) in TP‐treated mice had detrimental effects on fetal and placental development and compromised hormone synthesis. Importantly, E2, but not T0, actively enhanced melatonin synthetase AANAT expression and melatonin production in primary human trophoblast (PHT) cells through GPER1‐PKA‐CREB signaling pathway. On the other hand, melatonin suppressed the level of estrogen synthetase aromatase while promoting the expressions of androgen synthetic enzymes including 17β‐HSD3 and 3β‐HSD1 in PHT cells. These findings reveal an orchestrated feedback mechanism that maintains homeostasis of placental sex hormones and melatonin. It is implied that abnormal elevation of T0 synthesis likely serves as the primary cause of placental endocrine disturbances associated with PE. The suppression of melatonin may represent an adaptive strategy to correct the imbalance in sex hormone levels within preeclamptic placentas. The findings of this study offer novel evidence that identifies potential targets for the development of innovative therapeutic strategies for PE. [ABSTRACT FROM AUTHOR]

We study the concurrence for arbitrary N-partite W-class states based on the (N - 1) -partite partitions of subsystems by taking account to the structures of W-class states. By using the method of permutation and combination, we give some analytical formulas of concurrence and elegant relations between the N-partite concurrence and the (N - 1) -partite concurrence for arbitrary N-partite W-class states. Applying these relations, we present better lower bounds of concurrence for some multipartite mixed states. An example is given to demonstrate that our lower bounds can detect more entanglements. [ABSTRACT FROM AUTHOR]

Ischemic stroke is a common type of stroke with a high mortality and morbidity rate. Preventing and controlling cerebral ischemic injury is particularly important. Forsythiaside A (FA) has been reported to have anti-inflammatory and antioxidant activities. The aim of the present study was to explore the impact of FA on middle cerebral artery occlusion (MCAO)-induced cerebral ischemic injury in rats. The results indicated that FA markedly increased the percent survival and decreased the neurological deficit score in rats with cerebral ischemic injury. Furthermore, cell apoptosis was significantly inhibited by FA administration, which was accompanied by decreased caspase-3 and caspase-9 expression. A marked increase in the expression levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone dehydrogenase 1 and glutathione-s-transferase was detected in FA-treated rats. In addition, treatment with FA reduced malonaldehyde expression, and enhanced the expression of superoxide dismutase and glutathione. Furthermore, endoplasmic reticulum (ER) stress was vastly alleviated by FA treatment, as evidenced by the increased expression of B-cell lymphoma 2, apoptosis regulator and the downregulated expression of phosphorylated (phospho)-protein kinase RNA-like ER kinase (PERK)/PERK, phospho-inositol-requiring enzyme 1 (IRE1α)/IRE1α and CCAAT-enhancer-binding proteins homologous protein. Taken together, the present study demonstrated that FA attenuated cerebral ischemic damage via mediation of the activation of Nrf2 and ER stress pathways. These data may provide ideas for novel treatment strategies of cerebral ischemic damage. [ABSTRACT FROM AUTHOR]

Abstract Directing differentiation of neural stem/progenitor cells (NSCs/NPCs) to produce functional neurons is one of the greatest challenges in regenerative medicine. Our previous paper has confirmed that electrical stimulation has a high efficiency of triggering neuronal differentiation by using isolated filum terminale (FT)-derived NPCs. To further clarify the intrinsic molecular mechanisms, protein–protein interaction (PPI) network analysis was applied to pinpoints novel hubs in electric field (EF)-induced neuronal differentiation. In this study, siRNA transfection of Achaete-scute homolog 1 (Ascl1) in NPCs or NPCs was followed by direct current stimulation at 150 mV/mm. Neuronal differentiation rate and protein expression level were analyzed after 7 or 14 days of electrical stimulation. The data showed that the expression level of Ascl1 was enhanced by electrical stimulation and positively correlated to EF strength. Moreover, we identified that the expression of Ascl1 positively regulated neuronal differentiation of NPCs and can be up-regulated by EF-stimulation through the activation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway. Therefore, this study provides new insights into the role of Ascl1 and its relevant PI3K/Akt pathway in regulating of EF-induced neuronal differentiation and pointed out that continuous expression of Ascl1 in NPCs is required for EF-induced neuronal differentiation. Graphical abstract Unlabelled Image Highlights • EF-induced neuronal differentiation correlated with Ascl1 expression level positively. • Continuous expression of Ascl1 in NPCs is necessary for EF-induced neuronal differentiation. • Ascl1 regulates EF-induced neuronal differentiation through PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]

Highlights • Integration of spray cooling with waste heat reusing and peak load shifting. • HCS exhibits excellent energy saving, exergy increase and operation cost saving. • Sensitivity analysis shows the importance of spray cooling inlet temperature. • Economic analysis shows a cost payback period as low as 286 days. Abstract A hybrid cooling system aimed at enhancing energy, exergy and economic efficiency of data center is proposed. The proposed system combines a high cooling efficiency spray cooling system, a waste heat reusing absorption chiller and a peak load shifting chilled water storage. This combination is implemented by replacing the condenser of spray cooling system with the generator of absorption chiller, and storing cooling capacity of absorption chiller during off-peak time to supplement the cooling load during on-peak time. A thermodynamic model is developed based on energy and exergy balance. Parametric sensitivity analysis is performed to investigate the effects of spray cooling inlet temperature, chilled water temperature, cooling water temperature and ambient temperature on the energy saving efficiency, exergy efficiency and operation cost. Comparison study and economic analysis are conducted based on Dawning 5000A supercomputer in Shanghai, China. Sensitivity analysis results show that the effect of spray cooling inlet temperature is the largest, while the effects of chilled water temperature and cooling water temperature are the smallest. At appropriate condition, the absorption chiller and chilled water storage could totally eliminated the cooling load of air conditioner during on-peak time. The energy saving efficiency, exergy efficiency and operation cost saving could be up to 51%, 17%, and 71% with the cost payback period as low as 286 days. [ABSTRACT FROM AUTHOR]

Background: Cerebral small vessel disease (CSVD) is a systemic disease, affecting not only the brain, but also eyes and other organs. The total CSVD score is a tool for comprehensive evaluation of brain lesions in patients with CSVD. The ophthalmic artery (OA) is a direct response to ocular blood flow. However, little is known about the correlation between CSVD and characteristics of OA. We investigated the OA morphologies and hemodynamics in patients with CSVD and the correlation between these changes and the total CSVD score. Methods: This cross-sectional observational study included 34 eyes from 22 patients with CSVD and 10 eyes from 5 healthy controls. The total CSVD score was rated according to the CSVD signs on magnetic resonance imaging. OA morphological characteristics were measured on the basis of 3D OA model reconstruction. OA hemodynamic information was calculated using computational fluid dynamics simulations. Results: The total CSVD score negatively correlated with the OA diameter, blood flow velocity, and mass flow ratio (all P < 0.05). After adjusting for potential confounding factors, the total CSVD score was still independently correlated with the OA blood velocity (β = − 0.202, P = 0.005). The total CSVD score was not correlated with OA angle (P > 0.05). The presence of cerebral microbleeds and enlarged perivascular spaces was correlated with the OA diameter (both P < 0.01), while the lacunar infarcts and white matter hyperintensities were correlated with the OA blood velocity (both P < 0.001). Conclusions: The decrease of the blood velocity in the OA was associated with the increase in the total CSVD score. The changes of the OA diameter and velocity were associated with the presence of various CSVD signs. The findings suggest that more studies are needed in the future to evaluate CSVD by observing the morphologies and hemodynamics of OA. [ABSTRACT FROM AUTHOR]

Thyroid-associated ophthalmopathy (TAO) is an autoimmune disease. Studies showed that T helper 1 (Th1), Th2, and Th17 cells play important roles in the pathology of TAO. Tim-3 and its only known ligand Galectin-9 (Gal-9) is related to the suppression of Th1 and Th17 cytokine secretion. This study aims to investigate the role of Tim3/Gal-9 in the inflammatory response of TAO. In this study, the levels of Tim3, Gal-9, and cytokines of Th1 (TNF-α and IFN-γ), Th2 (IL-4), and Th17 (IL-17) cells were analyzed in the blood samples of TAO patients and healthy controls as well as in orbital fibroblasts. Tim3 overexpression and Gal-9 neutralizing antibody were used in TAO and LPS-stimulated control orbital fibroblasts to further investigate the role and mechanism of Tim3/Gal-9 on the inflammation of TAO. We found Tim3 and Gal-9 expression was significantly downregulated in TAO patients and further lower in active TAO than inactive TAO or controls. Th1, Th2, and Th17 cytokines were all increased in TAO patients. Th1 and Th17 cytokines were higher in active TAO patients than in inactive TAO patients, while Th2 cytokines were enhanced in inactive TAO. Tim3 overexpression decreased the levels of Th1 and Th17 cytokines, but not Th2 cytokine in TAO or LPS-stimulated control orbital fibroblasts. These effects were abrogated by Gal-9 neutralizing antibody. Moreover, Tim3 reduced the levels of p -Akt and p-p65 in TAO or LPS-induced control orbital fibroblasts that were reversed by Gal-9 blocking. In conclusion, Tim3/Gal-9 alleviates the inflammation of TAO patients via suppressing Akt/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Purpose: To determine the molecular mechanisms underlying ocular ischemic syndrome (OIS). This study uses a rat model to evaluate the role of the RhoA/MEK1/ ERK1/2/iNOS pathways in response to OIS-associated oxidative and nitrosative stress, with a long-term goal of identifying therapeutic targets for OIS. Methods: Rats were randomly allocated to one of three groups: bilateral occlusion of the common carotid artery (BOCCA), sham surgery control, or unoperated control (n = 8/group). Three months after the procedure, retinas were analyzed anatomically, using immunohistochemistry and by enzyme-linked immunosorbent assay for RhoA, MEK1, ERK1, ERK2, iNOS. Retinal injury was assessed using TUNEL. Levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by WST-1 and TBA methods, respectively. Results: In BOCCA rats, occlusion of the bilateral common carotid artery induced degeneration of retinal ganglion cells, which was not observed in either control group. Retinal levels of RhoA, MEK1, ERK1, ERK2, iNOS, NOX2, and MDA were elevated in the BOCCA group, but not in either control group. In comparison, retinal levels of SOD were reduced in SOD animals. By immunofluorescent staining, RhoA was elevated in all retinal layers, while the increased levels of MEK, ERK1/1, and NOX were restricted to the INL, and that of ERK1/2 and NOX inner nuclear layer; iNOS elevations were observed in both the inner and outer nuclear layers. TUNEL labeling results showed that BOCCA group is higher staining than sham and control group. Conclusions: OIS elevates activity of the RhoA/MERK1/ERK1/2/iNOS pathways throughout the retina, likely reflecting a response to oxidative and nitrosative stress. Retinal thickness was reduced in BOCCA rats, reflecting a loss of retinal ganglion cells following the reduced blood flow to the eye. These results indicate that drugs that inhibit these pathways may be effective treatments for OIS. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) -induced adverse events (AEs) have been reported affecting almost all human organs. However, studies about ocular AEs are few. A meta-analysis was performed to evaluate the risks of ICI-related ophthalmic AEs compare to chemotherapy. Methods: Eligible studies were selected from phase II/III randomized controlled trials investigating ICIs. The data were analyzed by R software and Stata. Odds ratio of treatment-related AE (trAEs) and nonspecific ophthalmic trAEs (NS-trAEs) were lower for PD-1/PD-L1 inhibitors than chemotherapy (OR 0.44, p <.05; OR 0.28, p <.001; OR 0.18, p <. 05; OR: 0.18, p <.001respectively). Compared with monotherapy, PD-1 plus CTLA-4 inhibitors increased the risks of immune-related AEs (irAEs) (OR 4.52, p <.01); ICIs plus chemotherapy increased the risks of trAEs and irAEs (OR 2.82, p <.001; OR 3.63, p <.05 respectively). PD-L1/PD-1 inhibitors had lower risks of trAEs and NS-trAEs than chemotherapy; Compared with monotherapy, combination therapy had higher risks of ophthalmic trAEs and irAEs. PD-1: programmed cell death protein 1; PD-L1: programmed cell death protein ligand 1; CTLA-4: cytotoxic T-lymphocyte-associated protein 4; ICI: immune checkpoint inhibitor; AE: adverse event; trAE: treatment-related adverse event;irAE: immune-related adverse events; NS-trAE: nonspecific ophthalmic treatment-related adverse event; RCT: randomized controlled trials; PFS: progression-free survival; OS: overall survival; ORR: objective response rate; MM: melanoma; NSCLC: non-small cell lung cancer; SCLC: small cell lung cancer; HNSCC: head-neck squamous cell carcinoma; PICOL: patient, intervention, comparison, and outcome; Versus: VS; Chem: chemotherapy; 95%CI: 95% confidence interval; FEM: fixed-effects model; REM: random-effects model; NA: not applicable; MeSH: medical subject heading [ABSTRACT FROM AUTHOR]

In the title compound, (C4H12N)2[Cu(C3S5)2], the CuII atom lies on a centre of inversion and is coordinated by four S atoms from two 2-thioxo-1,3-dithiole-4,5-dithiol­ate ligands in a square-planar geometry. [ABSTRACT FROM AUTHOR]

In the title complex, (C6H8N)2[Cd(C3S5)2], the CdII ion is coordinated by four dmit (2-thioxo-1,3-dithione-4,5-dithiol­ate) S atoms in a distorted tetra­hedral geometry. The N-methyl­pyridinium cations link with the CdII complex anion via weak C—H⋯S hydrogen bonding. [ABSTRACT FROM AUTHOR]

• The CWT and DWT spectrographs of GIC and dBx/dt during the 17 March 2013 storm are very similar. • The XWT and WTC spectra of GIC and dBx/dt reveal their correlation and phase relationship for the first time. • The third-order low frequency coefficient best reflects the disturbances in GIC and dBx/dt. Geomagnetically induced current (GIC) is known to be closely related to the rate of change of local horizontal magnetic field (dBx/dt); and their spectra can give better insight into the relationship. We study the spectral characteristics of GIC measured in Finland and dBx/dt measured 30 km away during the 17 March 2013 intense geomagnetic storm (SymHMin = −132 nT). Two bursts of large GIC (up to 32A) and dBx/dt occurred at ∼16 UT and 18 UT during the storm main phase. For the first time, the cross wavelet transform (XWT) and wavelet coherence (WTC) techniques are used to investigate the correlation and phase relationship of GIC and dBx/dt in time-frequency domain. Their WTC correlation is strong (over 0.9) over the entire storm period, indicating dBx/dt is the main factor causing GIC. Their XWT spectra show two enclosed periods (8–42 min and 2–42 min) in the high energy region corresponding to the two bursts of activity in GIC and dBx/dt. Morever, we use continuous wavelet transform (CWT) and discrete wavelet transform (DWT) to analyze the spectral characteristics of GIC and dBx/dt. It is found that the CWT and DWT spectra of the two are very similar, especially in the low frequency characteristics, without continuous periodicity. Wavelet coefficients become large when GIC and dBx/dT are large; and the third-order coefficient, which corresponds to low-frequency part, best reflects the disturbance of GIC and dBx/dt. [ABSTRACT FROM AUTHOR]

Because heavy metals (HMs) occurring naturally in soils accumulate continuously due to human activities, identifying and apportioning their sources becomes a challenging task for pollution prevention in urban environments. Besides the enrichment factors (EFs) and principal component analysis (PCA) for source classification, the receptor model (Absolute Principal Component Scores-Multiple Linear Regression, APCS-MLR) and Pb isotopic mixing model were also developed to quantify the source contribution for typical HMs (Cd, Co, Cr, Cu, Mn, Ni, Pb, Zn) in urban park soils of Xiamen, a representative megacity in southeast China. Furthermore, distribution patterns of their concentrations and sources in 13 soil profiles (top 20 cm) were investigated by different depths (0–5, 5–10, 10–20 cm). Currently the principal anthropogenic source for HMs in urban soil of China is atmospheric deposition from coal combustion rather than vehicle exhaust. Specifically for Pb source by isotopic model ( 206 Pb/ 207 Pb and 208 Pb/ 207 Pb), the average contributions were natural (49%) > coal combustion (45%) ≫ traffic emissions (6%). Although the urban surface soils are usually more contaminated owing to recent and current human sources, leaching effects and historic vehicle emissions can also make deep soil layer contaminated by HMs. [ABSTRACT FROM AUTHOR]

This work investigated the improvement in biomass yield and production and organics reduction of Rubrivivax gelatinosus ( R. gelatinosus ) by adding magnesium (Mg 2+ ) for sewage purification under natural light micro-oxygen conditions. The results showed that with the optimal Mg 2+ dosage (10 mg/L), biomass production (4125.6 mg/L) was enhanced by 59%. The biomass yield was improved by 43.3%. COD and protein removal increased more than 90%. Hydraulic retention time was decreased by 25%. Moreover, 5–10 mg/L Mg 2+ improved R. gelatinosus yield in wastewater to medium levels. Analyses revealed that different Mg 2+ concentrations had different mechanisms for impacting biomass production and COD removal. This was because there was an upper limit (15 mg/L) and an optimal value (6 mg/L) of intracellular Mg 2+ concentrations for R. gelatinosus . Appropriate Mg 2+ concentrations enhanced ATP production, which improved the secretion and activity of protease, indicating that more protein and COD were removed and more biomass accumulated. However, excessive Mg 2+ was harmful for biomass accumulation and COD removal because excess Mg 2+ decreased ATP production. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia (PE), a placenta-associated pregnancy complication, is the leading cause of maternal and perinatal morbidity and mortality. Met/Erk signaling is inhibited in the placentas of patients with early-onset preeclampsia (E-PE), but the underlying mechanisms remain elusive. In this study, the expression modes of Met and endocytic vesicles in normal and preeclamptic placentas were compared. Biotinylation internalization/recycling assays were used to measure the endocytosis of Met under hypoxia and normoxia in HTR8/SVneo cells. In addition, the expression level of Cbl, a specific E3 ligase of Met, was measured under hypoxia and normoxia, and the endocytosis of Met was studied by using confocal microscopy. Results: We found considerable intracellular accumulation of Met, which was colocalized with caveolin-1 (CAV-1), in trophoblasts from E-PE placentas. Prolonged hypoxic stimulation led to the remarkable augmentation of CAV-1-mediated Met endocytosis in HTR8/SVneo cells. In addition, the expression of Cbl was substantially repressed by sustained hypoxia, disrupting ubiquitin degradation and the subsequent intracellular accumulation of Met in HTR8/SVneo cells. The abnormal degradation of Met hampered the ability of hepatocyte growth factor (HGF) to promote trophoblast cell invasion. In E-PE placentas, aberrant upregulation of CAV-1 and downregulation of Cbl were observed in parallel to the intracellular accumulation of Met. Conclusions: These findings reveal that prolonged hypoxic stress induces the augmentation of endocytosis and repression of ubiquitin-mediated Met degradation, which leads to the impaired regulation of trophoblast invasion by HGF/Met signaling. These data provide novel evidence for elucidating the pathogenesis of preeclampsia, especially of the early-onset subtype. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is one of the main causes for the death of pregnant women. The developmental disorders of placental trophoblastic cells are related to the pathogenesis of PE. The malfunction of placenta may result in a high oxidative stress at the feto-maternal interface, which stimulates the excessive production of various factors from placenta. Those soluble placental factors are released into maternal circulation, eventually leading to the maternal symptoms of PE. Those hormones and molecules secreted by placenta, such as VEGF and anti -VEGF, methoxyestradiol, atrial natriuretic peptide, activin A and inhibin A, could partly reflect the developmental disorders of placenta. miRNAs and genetics were also found to be related to the pathogenesis of PE. [ABSTRACT FROM AUTHOR]

Objectives: Success in pregnancy in mammals predominantly depends on a well‐developed placenta. The differentiation of invasive trophoblasts is a fundamental process of placentation, the abnormalities of which are tightly associated with pregnancy disorders including preeclampsia (PE). Monoclonal nonspecific suppressor factor beta (MNSFβ) is an immunosuppressive factor. Its conventional knockout in mice induced embryonic lethality, whereas the underlying mechanism of MNSFβ in regulating placentation and pregnancy maintenance remains to be elucidated. Methods: Trophoblast‐specific knockout of MNSFβ was generated using Cyp19‐Cre mice. In situ hybridization (ISH), haematoxylin and eosin (HE), immunohistochemistry (IHC) and immunofluorescence (IF) were performed to examine the distribution of MNSFβ and insulin‐like growth factor 2 mRNA‐binding protein 2 (IGF2BP2) at the foeto‐maternal interface. The interaction and expression of MNSFβ, IGF2BP2 and invasion‐related molecules were detected by immunoprecipitation (IP), immunoblotting and quantitative real‐time polymerase chain reaction (qRT‐PCR). The cell invasion ability was measured by the Transwell insert assay. Results: We found that deficiency of MNSFβ in trophoblasts led to embryonic growth retardation by mid‐gestation and subsequent foetal loss, primarily shown as apparently limited trophoblast invasion. In vitro experiments in human trophoblasts demonstrated that the conjugation of MNSFβ with IGF2BP2 and thus the stabilization of IGF2BP2 essentially mediated the invasion‐promoting effect of MNSFβ. In the placentas from MNSFβ‐deficient mice and severe preeclamptic (PE) patients, downregulation of MNSFβ was evidently associated with the repressed IGF2BP2 expression. Conclusions: The findings reveal the crucial role of MNSFβ in governing the trophoblast invasion and therefore foetal development, and add novel hints to reveal the placental pathology of PE. [ABSTRACT FROM AUTHOR]

The maternal recognition of pregnancy is a necessary prerequisite for gestation maintenance through prolonging the corpus luteum lifespan and ensuring progesterone production. In addition to pituitary prolactin and placental lactogens, decidual derived prolactin family members have been presumed to possess luteotropic effect. However, there was a lack of convincing evidence to support this hypothesis. Here, we unveiled an essential role of uterine Notch2 in pregnancy recognition and corpus luteum maintenance. Uterine-specific deletion of Notch2 did not affect female fertility. Nevertheless, the expression of decidual Prl8a2, a member of the prolactin family, was downregulated due to Notch2 ablation. Subsequently, we interrupted pituitary prolactin function to determine the luteotropic role of the decidua by employing the lipopolysaccharide-induced prolactin resistance model, or blocking the prolactin signaling by prolactin receptor-Fc fusion protein, or repressing pituitary prolactin release by dopamine receptor agonist bromocriptine, and found that Notch2-deficient females were more sensitive to these stresses and ended up in pregnancy loss resulting from abnormal corpus luteum function and insufficient serum progesterone level. Overexpression of Prl8a2 in Notch2 knockout mice rescued lipopolysaccharide-induced abortion, highlighting its luteotropic function. Further investigation adopting Rbpj knockout and DNMAML overexpression mouse models along with chromatin immunoprecipitation assay and luciferase analysis confirmed that Prl8a2 was regulated by the canonical Notch signaling. Collectively, our findings demonstrated that decidual prolactin members, under the control of uterine Notch signaling, assisted pituitary prolactin to sustain corpus luteum function and serum progesterone level during post-implantation phase, which was conducive to pregnancy recognition and maintenance. Author summary: Progesterone secreted from the corpus luteum in the ovary is indispensable to preg-nancy maintenance in both rodents and humans. Therefore, prolonged corpus lute-um lifespan and sustainable progesterone production is a prerequisite for a success-ful pregnancy. In rodents, in addition to pituitary prolactin and placental lactogens, decidual derived factors have been presumed to possess luteotropic effects during the post-implantation stage. In this study, utilizing a mouse model with uterine spe-cific deletion of Notch2, which displayed decreased level of decidual prolactin mem-ber Prl8a2, combined with multiple approaches to interrupt the pituitary prolactin signal, we demonstrated that decidual derived Prl8a2 assisted pituitary prolactin to sustain corpus luteum function and serum progesterone level during post-implantation phase, which was conducive to pregnancy recognition and mainte-nance. In addition, the expression of decidual Prl8a2 was under the direct control of the canonical Notch pathway. Together, we herein provide convincing evidence that decidual produced Prl8a2, modulated by uterine canonical Notch signaling, exhibits luteo-tropic functions and contributes to pregnancy maintenance. [ABSTRACT FROM AUTHOR]

The implant containing Nestorone is a promising long-acting contraceptive especially suitable for lactating women. In this study, two experiments were designed to observe the effect of Nestorone on the gonadotropic cells in pituitary of rats for analyzing its antiovulation mechanism. In the first experiment, the ED50 of Nestorone on inhibiting ovulation was found to be 1.32 mg/kg. The serum luteinizing hormone (LH) levels were significantly lower 60 h after being treated with Nestorone at 8:30–9:00 a.m. on Day 2 (D2) of estrus. Image analysis showed that the average size of the LH cells in groups treated with Nestorone at 2 or 4 mg/kg was larger than that of the control. In the group treated with 4 mg/kg, most of gonadotropic cells were regular round in shape. And, abundant granules in cytoplasm were found in those cells, which indicated that the LH stored in cells was not released. In the second experiment, the rats were treated with Nestorone at 5 mg/kg at 11:30–12:00 a.m. on D2 of estrus. The normal or higher expression of LHβ mRNA in pituitary suggested that the synthesis of LH was not inhibited by the treatment with Nestorone. The expression of PR mRNA in pituitary was significantly lower than that of the control at 33 h after treatment. This might be a direct effect of Nestorone, since there were no differences in the serum E2 and P4 levels between the treated and the control group. It is concluded that Nestorone prevents ovulation through inhibition of LH secretion and it has no effect on synthesis of LH. Progesterone receptors in pituitary might be involved in this process, but further study is needed to gain more evidence. [Copyright &y& Elsevier]

Different functional regions of brain are fundamental for basic neurophysiological activities. However, the regional specification remains largely unexplored during human brain development. Here, by combining spatial transcriptomics (scStereo-seq) and scRNA-seq, we built a spatiotemporal developmental atlas of multiple human brain regions from 6–23 gestational weeks (GWs). We discovered that, around GW8, radial glia (RG) cells have displayed regional heterogeneity and specific spatial distribution. Interestingly, we found that the regional heterogeneity of RG subtypes contributed to the subsequent neuronal specification. Specifically, two diencephalon-specific subtypes gave rise to glutamatergic and GABAergic neurons, whereas subtypes in ventral midbrain were associated with the dopaminergic neurons. Similar GABAergic neuronal subtypes were shared between neocortex and diencephalon. Additionally, we revealed that cell-cell interactions between oligodendrocyte precursor cells and GABAergic neurons influenced and promoted neuronal development coupled with regional specification. Altogether, this study provides comprehensive insights into the regional specification in the developing human brain. [Display omitted] • Spatiotemporal developmental atlas of distinct human brain regions is built • Heterogeneous RG subtypes with specific spatial distribution are revealed • RG regional heterogeneity contributes to the regional specification of neurons • Interactions between OPCs and GABAergic neurons promote regional specification A spatiotemporal developmental atlas of human brain development including scStereo-seq analysis covering multiple time points between GW6 and GW16 as well as scRNA-seq across multiple brain regions spanning GW6 to GW23 is reported. [ABSTRACT FROM AUTHOR]

Background: Macrosomia is a major adverse pregnancy outcome of gestational diabetes mellitus (GDM). Although BMI, symphysis-fundal height (SFH) and abdominal circumference (AC) are associated with foetal weight, there are some limitations to their use, especially for the prediction of macrosomia. This study aimed to identify a novel predictive methodology to improve the prediction of high-risk macrosomia.Methods: Clinical information was collected from 3730 patients. The association between the ISFHAC (index of the SFH algorithm multiplied by the square of AC) and foetal weight was determined and validated. A new index, the ISFHAC, was evaluated by area under the curve (AUC) analysis.Results: A total of 1087 GDM and 657 normal singleton pregnancies were analysed. The ISFHAC was positively correlated with foetal weight in GDM pregnancies and normal pregnancies (NPs). The AUCs of the ISFHAC were 0.815 in the GDM group and 0.804 in the NP group, which were higher than those of BMI, SFH, AC and GA. The ISFHAC cut-off points were 41.7 and 37 in the GDM and NP groups, respectively. The sensitivity values for the prediction of macrosomia with high ISFHAC values were 75.9 and 81.3% in the GDM and NP groups, respectively, which were higher than those with BMI. Regarding the validation data, the sensitivity values for prediction with high ISFHAC values were 78.9% (559 GDM pregnancies) and 78.3% (1427 NPs).Conclusions: The ISFHAC can be regarded as a new predictor of and risk factor for macrosomia in GDM pregnancy and NP. [ABSTRACT FROM AUTHOR]

Background: Endoscopic biliary stenting by endoscopic retrograde cholangiopancreatography (ERCP) is the most common form of palliation for malignant hilar obstruction. However, ERCP in such cases is associated with a risk of cholangitis. The incidence of post-ERCP cholangitis is particularly high in Bismuth type IV hilar obstruction, and this risk is further increased when the contrast injected for cholangiography is not drained. The present study aims to compare the incidence of cholangitis associated with the use of a contrast agent, air and CO2 for cholangiography in type IV hilar biliary lesions.Methods: The clinical data of consecutive 70 patients with type IV hilar obstruction, who underwent ERCP from October 2013 to November 2017, were retrospectively analyzed. These patients were divided into three groups based on the agent used for cholangiography: group A, contrast (n = 22); group B, air (n = 18); group C, CO2 (n = 30). These three methods of cholangiography were chronologically separated. Prior to the ERCP, MRCP was obtained from all patients to guide the endoscopic intervention.Results: At baseline, there was no significant difference in terms of the patient's age, gender, symptoms and liver function tests among the three groups (P > 0.05). The complication rates were significantly higher in group A than in groups B and C (63.6% vs. 26.7 and 27.8%, P < 0.05). The incidence of post-ERCP cholangitis was significantly higher in group A (P < 0.05), while the incidence of post-ERCP pancreatitis and bleeding were similar in the three groups. After the ERCP, the mean hospital stay was shorter in groups B and C, when compared to group A (P < 0.05). However, there was no significant difference in the 30-day mortality rate among the three groups (P > 0.05). Furthermore, there was no significant difference between groups B and C in terms of primary end points.Conclusion: CO2 or air cholangiography during ERCP for type IV hilar obstruction is associated with reduced risk of post-ERCP cholangitis, when compared to conventional contrast agents. [ABSTRACT FROM AUTHOR]

Objectives: During human pregnancy, the endothelial cells of the uterine spiral arteries (SPA) are extensively replaced by a subtype of placental trophoblasts, endovascular extravillous trophoblasts (enEVTs), thus establishing a placental‐maternal circulation. On this pathway, foetus‐derived placental villi and enEVTs bath into the maternal blood that perfuses along SPA being not attacked by the maternal lymphocytes. We aimed to reveal the underlying mechanism of such immune tolerance. Methods: In situ hybridization, immunofluorescence, ELISA and FCM assay were performed to examine TGF‐β1 expression and distribution of regulatory T cells (Tregs) along the placental‐maternal circulation route. The primary enEVTs, interstitial extravillous trophoblasts (iEVTs) and decidual endothelial cells (dECs) were purified by FACS, and their conditioned media were collected to treat naïve CD4+ T cells. Treg differentiation was measured by FLOW and CFSE assays. Results: We found that enEVTs but not iEVTs or dECs actively produced TGF‐β1. The primary enEVTs significantly promoted naïve CD4+ T‐cell differentiation into immunosuppressive FOXP3+ Tregs, and this effect was dependent on TGF‐β1. In recurrent spontaneous abortion (RSA) patients, an evidently reduced proportion of TGF‐β1–producing enEVTs and their ability to educate Tregs differentiation were observed. Conclusions: Our findings demonstrate a unique immune‐regulatory characteristic of placental enEVTs to develop immune tolerance along the placental‐maternal circulation. New insights into the pathogenesis of RSA are also suggested. [ABSTRACT FROM AUTHOR]

Pre‐eclampsia (PE) is a serious hypertensive disorder of pregnancy that remains a leading cause of perinatal and maternal morbidity and mortality worldwide. Placental ischemia/hypoxia and the secretion of soluble fms‐like tyrosine kinase 1 (sFlt1) into maternal circulation are involved in the pathogenesis of PE. Although low‐dose aspirin (LDA) has beneficial effects on the prevention of PE, the exact mechanisms of action of LDA, particularly on placental dysfunction, and sFlt1 release, have not been well investigated. This study aimed to determine whether LDA exists the protective effects on placental trophoblast and endothelial functions and prevents PE‐associated sFlt1 release. First, we observed that LDA mitigated hypoxia‐induced trophoblast apoptosis, showed positive effects on trophoblast cells migration and invasion activity, and increased the tube‐forming activity of human umbilical vein endothelial cells (HUVECs). In addition, LDA decreased hypoxia‐induced sFlt1 production, and the c‐Jun NH2‐terminal kinase/activator protein‐1 (JNK/AP‐1) pathway was shown to mediate the induction of sFlt1. Moreover, the transcription factor AP‐1 was confirmed to regulate the Flt1 gene expression by directly binding to the Flt1 promoter in luciferase assays. The result of chromatin immunoprecipitation assays further demonstrated that LDA could directly decrease the expression of the transcription factor AP‐1, and thus decrease sFlt1 production. Finally, the effects of LDA on sFlt1 production were proved in human placental explants. Taken together, our data show the protective effects of LDA against trophoblast and endothelial cell dysfunction and reveal that the LDA‐mediated inhibition of sFlt1 via the JNK/AP‐1 pathway may be a potential cellular/molecular mechanism for the prevention of PE. [ABSTRACT FROM AUTHOR]