Next generation of immune checkpoint molecules in maternal-fetal immunity.

Successful pregnancy is a unique situation requires the maternal immune system to recognize and tolerate a semi-identical fetus and allow normal invasion of trophoblast cells. Although efforts have been made, the deep mechanisms of the maternal-fetal crosstalk have not yet been fully deciphered. Immune checkpoint molecules (ICMs) are a group of negative modulators of the immune response that avoid immune damage. They have been extensively studied in the fields of oncology and transplantation, while the latest evidence suggests that they are closely associated with pregnancy outcomes via multiple inhibitory mechanisms. Although studies have mostly demonstrated the regulatory role of the well-known PD-1, CTLA-4 at the maternal-fetal interface, what is unique about the newly discovered multiple ICMs remains a mystery. Here, we review the latest knowledge on ICMs, focusing on the first generation of checkpoints (PD-1, CTLA-4) and the next generation (Tim-3, Tigit, Lag-3, VISTA) highlighting their immunoregulatory roles in maternal-fetal tolerance and decidual vascular remodeling, and their involvement in pathological pregnancies. The content covers three aspects: the characteristics they possess, the dynamic expression profile of their expression at the maternal-fetal interface, and their involvement in pathological pregnancy. In immunotherapy strategies for pregnancy complications, upregulation of immune checkpoints may play a role. Meanwhile, the impact on pregnancy outcomes when using ICMs in clinical cancer treatment during pregnancy is a topic worth exploring. These may serve as a guide for future basic research and clinical applications of maternal-fetal immunity.

Deep ancestral introgressions between ovine species shape sheep genomes via argali-mediated gene flow.

Previous studies reveal extensive genetic introgression between Ovis species, which affects genetic adaptation and morphological traits. However, the exact evolutionary scenarios underlying the hybridization between sheep and allopatric wild relatives remain unknown. To address this problem, we here integrate the reference genomes of several ovine and caprine species: domestic sheep, argali, bighorn sheep, snow sheep, and domestic goats. Additionally, we use 856 whole genomes representing 169 domestic sheep populations and their 6 wild relatives: Asiatic mouflon, urial, argali, snow sheep, thinhorn sheep and bighorn sheep. We implement a comprehensive set of analyses to test introgression among these species. We infer that the argali lineage originated ca. 3.08-3.35 Mya and hybridized with the ancestor of Pachyceriforms (e.g., bighorn sheep and snow sheep) at ∼1.56 Mya. Previous studies show apparent introgression from North American Pachyceriforms into the Bashibai sheep, a Chinese native sheep breed, despite their wide geographic separation. We show here that, in fact, the apparent introgression from the Pachyceriforms into Bashibai can be explained by the old introgression from Pachyceriforms into argali, and subsequent recent introgression from argali into Bashibai. Our results illustrate the challenges of estimating complex introgression histories and provide an example of how indirect and direct introgression can be distinguished.

Experimental study of modified Tavis-Cummings model with directly-coupled superconducting artificial atoms.

The Tavis-Cummings model is intensively investigated in quantum optics and has important applications in generation of multi-atom entanglement. Here, we employ a superconducting circuit quantum electrodynamic system to study a modified Tavis-Cummings model with directly-coupled atoms. In our device, three superconducting artificial atoms are arranged in a chain with direct coupling through fixed capacitors and strongly coupled to a transmission line resonator. By performing transmission spectrum measurements, we observe different anticrossing structures when one or two qubits are resonantly coupled to the resonator. In the case of the two-qubit Tavis-Cummings model without qubit-qubit interaction, we observe two dips at the resonance point of the anticrossing. The splitting of these dips is determined by Δ λ=2g12+g32, where g1 and g3 are the coupling strengths between Qubit 1 and the resonator, and Qubit 3 and the resonator, respectively. The direct coupling J12 between the two qubits results in three dressed states in the two-qubit Tavis-Cummings model at the frequency resonance point, leading to three dips in the transmission spectrum. In this case, the distance between the two farthest and asymmetrical dips, arising from the energy level splitting, is larger than in the previous case. The frequency interval between these two dips is determined by the difference in eigenvalues (Δ λ=ε 1+-ε 1-), obtained through numerical calculations. What we believe as novel and intriguing experimental results may potentially advance quantum optics experiments, providing valuable insights for future research.

Loophole-Free Test of Local Realism via Hardy's Violation.

Bell's theorem states that the quantum mechanical description of physical quantities cannot be fully explained by local realistic theories, laying a solid basis for various quantum information applications. Hardy's paradox is celebrated as the simplest form of Bell's theorem concerning its "All versus Nothing" approach to test local realism. However, due to experimental imperfections, existing tests of Hardy's paradox require additional assumptions of the experimental systems, and these assumptions constitute potential loopholes for faithfully testing local realistic theories. Here, we experimentally demonstrate Hardy's nonlocality through a photonic entanglement source. By achieving a detection efficiency of 82.2%, a quantum state fidelity of 99.10%, and applying high-speed quantum random number generators for the measurement setting switching, the experiment is implemented in a loophole-free manner. During 6 h of running, a strong violation of P_{Hardy}=4.646×10^{-4} up to 5 standard deviations is observed with 4.32×10^{9} trials. A null hypothesis test shows that the results can be explained by local realistic theories with an upper bound probability of 10^{-16348}. These testing results provide affirmative evidence against local realism, and establish an advancing benchmark for quantum information applications based on Hardy's paradox.

TMSOTf-Catalyzed C2-Sulfenylation of Indole Alkaloids Using N-Sulfenylsuccinimides: An Approach for the Total Synthesis of Isatindigotindolosides.

A TMSOTf-catalyzed C2-sulfenylation of indole alkaloids with N-sulfenylsuccinimides has been developed. This straightforward, metal-free, and cost-effective catalytic system produces valuable 2-thioindole derivatives with yields ranging from moderate to excellent. The synthetic applicability demonstrated includes the total syntheses of isatindigotindolosides I-IV.

{SeO2(OH)} Bridging Lanthanide-Containing Antimono-Seleno-Tungstates.

A series of new trigonal pyramidal {SeO2(OH)} bridging lanthanide-containing antimono-seleno-tungstates [H2N(CH3)2]8Na8Cs4H9[Ln2SeW4O11(OH)(H2O)4(SbW9O33)(SeW9O33)(Se1/2Sb1/2W9O33)]2·32H2O [Ln = Tb (1), Dy (2), Ho (3), Er (4)] have been prepared by the synthetic strategy of simultaneously using the antimonotungstate precursor and simple material in an acidic aqueous solution and structurally characterized by single-crystal X-ray diffraction, powder X-ray diffraction, IR spectrometry, and thermogravimetric analysis. Their molecular structures contain an unprecedented hexameric polyoxoanion [Ln2SeW4O11(OH)(H2O)4(SbW9O33)(SeW9O33)(Se1/2Sb1/2W9O33)]229- constituted by two equivalent trimeric subunits Ln2W4O9(H2O)4(SbW9O33)(SeW9O33)(Se1/2Sb1/2W9O33) bridged via two µ2-{SeO2(OH)} linkers. Furthermore, the catalytic oxidation of various aromatic sulfides and sulfur mustard simulant 2-chloroethyl ethyl sulfide (CEES) by compound 3 as the heterogeneous catalyst has been investigated, exhibiting high conversion and selectivity as well as good stability and recyclability.

Se-Rich Multinuclear Er-Containing Dawson-type Poly(selenotungstate).

A multinuclear Er-containing Dawson-type poly(selenotungstate) (poly(ST)) [H2N(CH3)2]12Na8Cs6H26 [Er12Se14W12O72(H2O)6(Se2W14O52)6]·78H2O (1) was made by the one-pot assembly with an excess SeO32- source in the reaction system. The polyoxoanion consists of an extremely rare Er12Se14W12O72(H2O)6 ({Er12Se14W12}) cluster core surrounded by six tetravacant Dawson-type Se2W14O52 ({Se2W14}) fragments, representing the most Se-containing Dawson-type structure so far. Notably, the {Er12Se14W12} cluster exhibits an interesting trefoil-shaped configuration, formed by the condensation of a central Er3Se2O6 ({Er3Se2}) cage with three Er3Se4W4O22(H2O)2 ({Er3Se4W4}) clusters. The catalytic performance of 1 was evaluated by the oxidative decontamination of 2-chloroethyl ethyl sulfide (CEES) into nontoxic 2-chloroethyl ethyl sulfoxide (CEESO), showing remarkable conversion and selectivity, as well as excellent reusability.

How does central-local interaction affect local environmental governance? Insights from the transformation of central environmental protection inspection in China.

In recent years, one of the most important and innovative policy initiatives introduced by the Chinese government in the field of environmental protection and ecological civilization construction is the Central Environmental Protection Inspection (CEPI). CEPI is seen as a vital tool to encourage local implementation of environmental protection responsibility. Over the course of its operation (eight years), CEPI has transformed from the "campaign" phase to the "convention" phase. It is noted that while provincial governments face a common high-pressure environment created by CEPI, governance scenarios, behaviors, and performance vary across the country significantly. To better understand local governments' environmental governance behaviors under the transformation of CEPI, an integrated analysis framework consisting of two key elements, "central dominance" and "local proactiveness", is constructed based on the central-local interactions under the principal-agent model. Based on this framework, we conducted a multi-case comparative analysis of four classic cases, with the following findings. (1) Along with the operation of CEPI and its transformation, the interaction between the central and local governments leads to four governance scenarios: "control-active cooperation", "control-passive cooperation", "guidance-active promotion", and "guidance-passive promotion". (2) Influenced by various factors such as pressure by the central government, local governments' capabilities and governance motivations, local governments form governance behaviors with varying degrees of proactiveness and autonomy. (3) After examining the governance performance of varying behaviors, it is found that local government's "active promotion" behavior can achieve higher governance effectiveness in the "convention" phase. Therefore, it is of policy implication that local governments should be guided to transit from "passive cooperation" to "active promotion". This paper has important guiding significance for understanding local environmental governance behaviors under strong top-down institutional pressure.

Discovery of N-(phenylsulfonyl)thiazole-2-carboxamides as potent α-glucosidase inhibitors.

In a search for novel nonsugar α-glucosidase inhibitors for diabetes treatment, a series of N-(phenylsulfonyl)thiazole-2-carboxamide derivatives were designed and synthesized, the α-glucosidase inhibitory activities were then evaluated. Several compounds with promising α-glucosidase inhibitory effects were identified. Among these, compound W24 which shows low cytotoxicity and good α-glucosidase inhibitory activity with an IC50 value of 53.0 ± 7.7 µM, is more competitive compared with the commercially available drug acarbose (IC50 = 228.3 ± 9.2 µM). W24 was identified as a promising candidate in the development of α-glucosidase inhibitors. Molecular docking studies and molecular dynamics simulation were also performed to reveal the binding pattern of the active compound to α-glucosidase, and the binding free energy of the best compound W24 was 36.3403 ± 3.91 kcal/mol.

Data-Independent Acquisition-Based Quantitative Proteomic Analysis Reveals Potential Salivary Biomarkers of Primary Sjögren's Syndrome.

Objective As primary Sj?gren's syndrome (pSS) primarily affects the salivary glands, saliva can serve as an indicator of the glands' pathophysiology and the disease's status. This study aims to illustrate the salivary proteomic profiles of pSS patients and identify potential candidate biomarkers for diagnosis.Methods The discovery set contained 49 samples (24 from pSS and 25 from age- and gender-matched healthy controls [HCs]) and the validation set included 25 samples (12 from pSS and 13 from HCs). Totally 36 pSS patients and 38 HCs were centrally randomized into the discovery set or to the validation set at a 2:1 ratio. Unstimulated whole saliva samples from pSS patients and HCs were analyzed using a data-independent acquisition (DIA) strategy on a 2D LC?HRMS/MS platform to reveal differential proteins. The crucial proteins were verified using DIA analysis and annotated using gene ontology (GO) and International Pharmaceutical Abstracts (IPA) analysis. A prediction model for SS was established using random forests.Results A total of 1,963 proteins were discovered, and 136 proteins exhibited differential representation in pSS patients. The bioinformatic research indicated that these proteins were primarily linked to immunological functions, metabolism, and inflammation. A panel of 19 protein biomarkers was identified by ranking order based on P-value and random forest algorichm, and was validated as the predictive biomarkers exhibiting good performance with area under the curve (AUC) of 0.817 for discovery set and 0.882 for validation set.Conclusions The candidate protein panel discovered may aid in pSS diagnosis. Salivary proteomic analysis is a promising non-invasive method for prognostic evaluation and early and precise treatments for pSS patients. DIA offers the best time efficiency and data dependability and may be a suitable option for future research on the salivary proteome.

[Active secondary metabolites from an endophytic fungus Fusarium solani MBM-5 of Datura arborea].

This study investigated the chemical and biological activity of the secondary metabolites from an endophytic fungus Fusa-rium solani MBM-5 of Datura arborea. A total of six alkenoic acid compounds, including a new compound and five known ones, were isolated from the ethyl acetate extract of F. solani MBM-5 by using the chromatographic methods(open ODS column chromatography, silica gel column chromatography, Sephadex LH-20, and semi-preparative HPLC). The structures of the compounds were identified by using their physical and chemical data, spectroscopic methods(UV, IR, NMR, and HR-ESI-MS), and Mosher's reaction, which were fusaridioic acid E(1), fusaridioic acid C(2), fusaridioic acid A(3), L660282(4), hymeglusin(5), and hymeglnone(6). Compound 1 is new. MTT assay and Griss method were used to evaluate the growth inhibition of all the compounds against two tumor cells, as well as their influence and anti-inflammatory action on the release of NO from LPS-induced RAW264.7 cells. The results showed that compound 5 had strong growth inhibition activity against A549 and HepG2 cell lines, with IC_(50) values of 4.70 and 13.57 µmol·L~(-1), respectively. Compounds 1 and 6 significantly inhibited the release of NO from LPS-induced RAW264.7 cells, with IC_(50) values of 77.00 and 70.33 µmol·L~(-1), respectively.

A Planar-Structured Dinuclear Cobalt(II) Complex with Indirect Synergy for Photocatalytic CO2-to-CO Conversion.

Dinuclear metal synergistic catalysis (DMSC) has been proved an effective approach to enhance catalytic efficiency in photocatalytic CO2 reduction reaction, while it remains challenge to design dinuclear metal complexes that can show DMSC effect. The main reason is that the influence of the microenvironment around dinuclear metal centres on catalytic activity has not been well recognized and revealed. Herein, we report a dinuclear cobalt complex featuring a planar structure, which displays outstanding catalytic efficiency for photochemical CO2-to-CO conversion. The turnover number (TON) and turnover frequency (TOF) values reach as high as 14457 and 0.40 s-1 respectively, 8.6 times higher than those of the corresponding mononuclear cobalt complex. Control experiments and theoretical calculations revealed that the enhanced catalytic efficiency of the dinuclear cobalt complex is due to the indirect DMSC effect between two CoII ions, energetically feasible one step two-electron transfer process by Co2 I,I intermediate to afford Co2 II,II(CO2 2-) intermediate and fast mass transfer closely related with the planar structure.

The dysfunction of hormone-sensitive lipase induces lipid deposition and reprogramming of nutrient metabolism in fish.

Hormone-sensitive lipase (HSL) is one of the rate-determining enzymes in the hydrolysis of TAG, playing a crucial role in lipid metabolism. However, the role of HSL-mediated lipolysis in systemic nutrient homoeostasis has not been intensively understood. Therefore, we used CRISPR/Cas9 technique and Hsl inhibitor (HSL-IN-1) to establish hsla-deficient (hsla-/-) and Hsl-inhibited zebrafish models, respectively. As a result, the hsla-/- zebrafish showed retarded growth and reduced oxygen consumption rate, accompanied with higher mRNA expression of the genes related to inflammation and apoptosis in liver and muscle. Furthermore, hsla-/- and HSL-IN-1-treated zebrafish both exhibited severe fat deposition, whereas their expressions of the genes related to lipolysis and fatty acid oxidation were markedly reduced. The TLC results also showed that the dysfunction of Hsl changed the whole-body lipid profile, including increasing the content of TG and decreasing the proportion of phospholipids. In addition, the systemic metabolic pattern was remodelled in hsla-/- and HSL-IN-1-treated zebrafish. The dysfunction of Hsl lowered the glycogen content in liver and muscle and enhanced the utilisation of glucose plus the expressions of glucose transporter and glycolysis genes. Besides, the whole-body protein content had significantly decreased in the hsla-/- and HSL-IN-1-treated zebrafish, accompanied with the lower activation of the mTOR pathway and enhanced protein and amino acid catabolism. Taken together, Hsl plays an essential role in energy homoeostasis, and its dysfunction would cause the disturbance of lipid catabolism but enhanced breakdown of glycogen and protein for energy compensation.

Dual-Functional Eu-Metal-Organic Framework with Ratiometric Fluorescent Broad-Spectrum Sensing of Benzophenone-like Ultraviolet Filters and High Proton Conduction.

The construction of attractive dual-functional lanthanide-based metal-organic frameworks (Ln-MOFs) with ratiometric fluorescent detection and proton conductivity is significant and challenging. Herein, a three-dimensional (3D) Eu-MOF, namely, [Eu4(HL)2(SBA)4(H2O)6]·9H2O, has been hydrothermally synthesized with a dual-ligand strategy, using (4-carboxypiperidyl)-N-methylenephosphonic acid (H3L = H2O3PCH2-NC5H9-COOH) and 4-sulfobenzoic acid monopotassium salt (KHSBA = KO3SC6H4COOH) as organic linkers. Eu-MOF showed ratiometric fluorescent broad-spectrum sensing of benzophenone-like ultraviolet filters (BP-like UVFs) with satisfactory sensitivity, selectivity, and low limits of detection in water/ethanol (1:1, v/v) solutions and real urine systems. A portable test paper was prepared for the convenience of actual detection. The potential sensing mechanisms were thoroughly analyzed by diversified experiments. The synergistic effect of the forbidden energy transfer from the ligand to Eu3+, the internal filtration effect (IFE), the formation of a complex, and weak interactions between the KHSBA ligand and BP-like UVFs is responsible for the ratiometric sensing effect. Meanwhile, Eu-MOF displayed relatively high proton conductivity of 2.60 × 10-4 S cm-1 at 368 K and 95% relative humidity (RH), making it a potential material for proton conduction. This work provides valuable guidance for the facile and effective design and construction of multifunctional Ln-MOFs with promising performance.

Detection of Rickettsia spp. and Anaplasma ovis in Melophagus ovinus from southern Xinjiang, China.

Melophagus ovinus is a hematophagous insect that is distributed worldwide and plays a crucial role in transmitting disease-causing pathogens. From June 2021 to March 2022, a total of 370 M. ovinus were collected from 11 sampling points in southern Xinjiang, China. The specimens were identified using morphological and molecular analyses. Rickettsia spp. and Anaplasma ovis were detected from all the samples using seven Rickettsia-specific genetic markers and the msp-4 gene of A. ovis. Approximately 11% of the M. ovinus specimens were positive for Rickettsia spp., and Candidatus Rickettsia barbariae was the most predominant species (35/41; 85.4%), while R. massiliae was least prevalent (6/41; 14.6%). Approximately 10.5% (39/370) of the M. ovinus specimens were positive for A. ovis of genotype III, which was co-detected with Candidatus R. barbariae in M. ovinus (3/370; 0.8%). To the best of our knowledge, this is the first report of the detection of R. massiliae and Candidatus R. barbariae in M. ovinus globally. The detection and control of insect-borne diseases originating from M. ovinus should be strengthened in southern Xinjiang, an area important to animal husbandry and production.

[Influence of cavity design on quality of margin and marginal adaptation and microleakage of all-ceramic CAD/CAM inlays].

OBJECTIVE: To investigate the influence of 135° and 90° cavity design on quality of margin and marginal adaptation and microleakage of all-ceramic computer aided design/computer aided manufacturing (CAD/CAM) inlays. METHODS: One hundred extracted human molars were prepared by criteria of buccal occlusal (BO) inlay. On the buccal, the mesial margin was prepared as 135° bevel while the distal margin was prepared as butt-joint. All-ceramic restorations were made in the Sirona CEREC AC CAD/CAM system with VitaBlocs Mark Ⅱ, Upcera UP.CAD, IPS e.max CAD, Upcera Hyramic and Lava Ultimate. The gaps between each inlay's mesial margin-abutment and distal margin-abutment were recorded under an optical microscope. Each inlay was adhered to the abutment and aged by thermal cycling for 10 000 times. Each specimen was cut into 3 slices after staining. Dye penetration was evaluated under an optical microscope for mesial and distal margins. RESULTS: Mean marginal integrity rate, mean marginal gap value and mean depth of microleakage of 135° margin of Group Upcera Hyramic and Lava Ultimate were significantly better than those of Group VitaBlocs Mark Ⅱ, Upcera UP.CAD and IPS e.max CAD(P < 0.05). Mean marginal gap value, mean depth of microleakage and scale of mean depth of microleakage of 90° margin of Group Upcera Hyramic and Lava Ultimate were significantly better than those of Group Upcera UP.CAD and IPS e.max CAD (P < 0.05) while mean marginal integrity rate was not significantly different (P>0.05). Mean marginal integrity rate of 90° margin was significantly better than that of 135° margin in each group (P < 0.05) while mean depth of microleakage between different margins was not significantly different in each group (P>0.05). Mean marginal gap value of 90° margin of Group VitaBlocs Mark Ⅱ and IPS e.max CAD was significantly better than that of 135° margin (P < 0.05) while there was not significant difference in other 3 groups between 90° and 135° margin (P>0.05). Scale of mean depth of microleakage of 135° margin of Group Upcera Hyramic and Lava Ultimate was significant better than that of 90° margin (P < 0.05) while there was not significantly different in other 3 groups between 90° and 135° margin (P>0.05). CONCLUSION: The mesial and distal margins of abutement of all-ceramic inlay should be prepared as butt-joint.

A General Synthesis of Mesoporous Hollow Carbon Spheres with Extraordinary Sodium Storage Kinetics by Engineering Solvation Structure.

Porous and hollow carbon materials have great superiority and prospects in electrochemical energy applications, especially for surface charge storage due to the high active surface. Herein, a general strategy is developed to synthesize mesoporous hollow carbon spheres (MHCS) with controllable texture and compositions by the synergistic effect of dopamine polymerization and metal catalysis (Cu, Bi, Zn). Mesoporous MHCS-Cu and MHCS-Bi are regular spheres, while mesoporous MHCS-Zn possesses an inward concave texture, and simultaneously has a very high surface area of 1675.5 m2 g-1 and lower oxygen content through the catalytic deoxygenation effect. MHCS-Zn displays an exceptional sodium storage kinetics and excellent long cycling life with 171.9 mAh g-1 after 2500 cycles at 5 A g-1 in compatible ether-based electrolytes. Such electrolyte enables enhanced solvated Na+ transport kinetics with appropriate electrostatic interactions at the surface of carbon anode as revealed by molecular dynamics simulations and molecular surface electrostatic potential calculations. Such an anode also displays basically constant capacity working at 0 °C, and still delivers 140 mAh g-1 at 3 A g-1 under -20 °C. Moreover, MHCS-Zn anode is coupled with Na3 V2 (PO4 )3 cathode to construct a hybrid capacitor, which exhibits a high energy density of 145 Wh Kg-1 at a very high power of 8009 W kg-1 .

CT Scans and Cancer Risks: A Systematic Review and Dose-response Meta-analysis.

BACKGROUND: There is still uncertainty on whether ionizing radiation from CT scans can increase the risks of cancer. This study aimed to identify the association of cumulative ionizing radiation from CT scans with pertaining cancer risks in adults. METHODS: Five databases were searched from their inception to November 15, 2020. Observational studies reporting cancer risks from CT scans in adults were included. The main outcome included quantified cancer risks as cancer case numbers in exposed/unexposed adult participants with unified converted measures to odds ratio (OR) for relative risk, hazard ratio. Global background radiation (2.4 mSv per year) was used as control for lifetime attribution risk (LAR), with the same period from incubation after exposure until survival to 100 years. RESULTS: 25 studies were included with a sum of 111,649,943 participants (mean age: 45.37 years, 83.4% women), comprising 2,049,943 actual participants from 6 studies with an average follow-up period as 30.1 years (range, 5 to 80 years); 109,600,000 participants from 19 studies using LAR. The cancer risks for adults following CT scans were inordinately increased (LAR adults, OR, 10.00 [95% CI, 5.87 to 17.05]; actual adults, OR, 1.17 [95%CI, 0.89 to 1.55]; combined, OR, 5.89 [95%CI, 3.46 to 10.35]). Moreover, cancer risks elevated with increase of radiation dose (OR, 33.31 [95% CI, 21.33 to 52.02]), and multiple CT scan sites (OR, 14.08 [95% CI, 6.60 to 30.05]). The risk of solid malignancy was higher than leukemia. Notably, there were no significant differences for age, gender, country, continent, study quality and studying time phrases. CONCLUSIONS: Based on 111.6 million adult participants from 3 continents (Asia, Europe and America), this meta-analysis identifies an inordinately increase in cancer risks from CT scans for adults. Moreover, the cancer risks were positively correlated with radiation dose and CT sites. The meta-analysis highlights the awareness of potential cancer risks of CT scans as well as more reasonable methodology to quantify cancer risks in terms of life expectancy as 100 years for LAR. PROSPERO TRIAL REGISTRATION NUMBER: CRD42019133487.

Glutamine Maintains Satellite Glial Cells Growth and Survival in Culture.

Satellite glial cells (SGCs) tightly surround neurons and modulate sensory transmission in dorsal root ganglion (DRG). At present, the biological property of primary SGCs in culture deserves further investigation. To reveal the key factor for SGCs growth and survival, we examined the effects of different culture supplementations containing Dulbecco's Modified Eagle Medium (DMEM)/F12, DMEM high glucose (HG) or Neurobasal-A (NB). CCK-8 proliferation assay showed an increased proliferation of SGCs in DMEM/F12 and DMEM/HG, but not in NB medium. Bax, AnnexinV, and propidium iodide (PI) staining results showed that NB medium caused cell death and apoptosis. We showed that glutamine was over 2.5 mM in DMEM/F12 and DMEM/HG, whereas it was absence in NB medium. Interestingly, exogenous glutamine application significantly reversed the poor proliferation and cell death of SGCs in NB medium. These findings demonstrated that DMEM/F12 medium was optimal to get high-purity SGCs. Glutamine was the key molecule to maintain SGCs growth and survival in culture. Here, we provided a novel approach to get high-purity SGCs by changing the key component of culture medium. Our study shed a new light on understanding the biological property and modulation of glial cells of primary sensory ganglia.

Cinnamaldehyde prevents intergenerational effect of paternal depression in mice via regulating GR/miR-190b/BDNF pathway.

Paternal stress exposure-induced high corticosterone (CORT) levels may contribute to depression in offspring. Clinical studies disclose the association of depressive symptoms in fathers with their adolescent offspring. However, there is limited information regarding the intervention for intergenerational inheritance of depression. In this study we evaluated the intervention of cinnamaldehyde, a major constituent of Chinese herb cinnamon bark, for intergenerational inheritance of depression in CORT- and CMS-induced mouse models of depression. Depressive-like behaviors were induced in male mice by injection of CORT (20 mg·kg-1·d-1, sc) for 6 weeks or by chronic mild stress (CMS) for 6 weeks. We showed that co-administration of cinnamaldehyde (10, 20, or 40 mg·kg-1·d-1, ig) for 6 weeks in F0 males prevented the depressive-like phenotypes of F1 male offspring. In addition, co-administration of cinnamaldehyde (20 mg·kg-1·d-1, ig) for 4 weeks significantly ameliorated depressive-like behaviors of chronic variable stress (CVS)-stimulated F1 offspring born to CMS mice. Notably, cinnamaldehyde had no reproductive toxicity, while positive drug fluoxetine showed remarkable reproductive toxicity. We revealed that CMS and CORT significantly reduced testis glucocorticoid receptor (GR) expression, and increased testis and sperm miR-190b expression in F0 depressive-like models. Moreover, pre-miR-190b expression was upregulated in testis of F0 males. The amount of GR on miR-190b promoter regions was decreased in testis of CORT-stimulated F0 males. Cinnamaldehyde administration reversed CORT-induced GR reduction in testis, miR-190b upregulation in testis and sperm, pre-miR-190b upregulation in testis, and the amount of GR on miR-190b promoter regions of F0 males. In miR-190b-transfected Neuro 2a (N2a) cells, we demonstrated that miR-190b might directly bind to the 3'-UTR of brain-derived neurotrophic factor (BDNF). In the hippocampus of F1 males of CORT- or CMS-induced depressive-like models, increased miR-190b expression was accompanied by reduced BDNF and GR, which were ameliorated by cinnamaldehyde. In conclusion, cinnamaldehyde is a potential intervening agent for intergenerational inheritance of depression, probably by regulating GR/miR-190b/BDNF pathway.