A Metal-Free Molecular Ferroelectric [4-Me-cyclohexylamine]ClO4 Introduced by Boat and Chair Conformations of Cyclohexylamine.

Organic ferroelectrics have received a great deal of interest due to their exclusive properties. However, organic ferroelectrics have not been fully explored, which hinders their practical application. Here, we presented a novel metal-free organic molecular ferroelectric [4-MCHA][ClO4 ] (1) (4-MCHA=trans-4-methylcyclohexylamine), which exhibits an above-room-temperature of 328 K. Strikingly, the single crystal structure analysis of 1 shows that the driving force of phase transition is related to the interesting chair-boat conformation change of 4-MCHA cation, in addition to the order-disorder transition of ClO4 - anion. Using piezoelectric response force microscopy (PFM), the presence of domains and the implemented polarization switching were clearly observed, which explicitly determined the presence of room-temperature ferroelectricity of 1. As far as we know, the ferroelectric phase transition mechanism attributed to the conformational change in a trans isomeric cation is very rare. This research enriched the path of designing ferroelectric materials and smart materials.

Alkali Metal Organic-Inorganic Hybrid Compounds with Different Crystal Dimensions Show Phase-Transition, Dielectric, and SHG Properties Based on a Quasi-Spherical Amine (1S,4S)-2,5-Diazabicyclo[2.2.1]heptane.

Reactions of a chiral and quasi-spherical molecule [1S,4S-2,5-2.2.1-H2dabch]I2 (1) with alkali metal halide MX (M = Na, K, Cs; X = Cl, Br) at room temperature produced a series of organic-inorganic hybrid (OIH) materials [1S,4S-2,5-2.2.1-H2dabch]NaBr3 (2), [1S,4S-2,5-2.2.1-H2dabch]CsCl3·H2O (3) and [1S,4S-2,5-2.2.1-H2dabch]KBr3·H2O (4). The single-crystal X-ray diffraction analysis revealed that the organic-inorganic framework structures comprised of the templating ligand and alkali metal halides (NaBr, CsCl, KBr) displayed dimensions spanning from one-dimensional (1D) to three-dimensional (3D). Moreover, the results of both differential scanning calorimetry (DSC) and dielectric measurements demonstrated that compounds 1-4 displayed reversible, high-temperature phase transitions and noticeable dielectric anomalies. In addition, the temperature-dependent second harmonic generation (SHG) results revealed crystals 1 and 3 can switch from the SHG-ON to the SHG-OFF state, which was proved by the variable-temperature X-ray diffraction. This research aims to streamline the exploration of multifunctional second harmonic generation (SHG) and dielectric materials that have been synthesized using chiral ligands and alkali metals. This will provide researchers with enhanced opportunities to delve further into this specific research domain.

Antimony Bromide Organic-Inorganic Hybrid Compound with a Long-Chain Diamine Showing Switchable Phase Transition and Second-Harmonic Generation Properties.

Organic-inorganic hybrid metal halides have attracted significant attention in recent years due to their excellent optoelectronic properties and potential applications in solar cells. Herein, the organic-inorganic hybrid molecule [N,N-dimethyl-1,3-propanediamine]SbBr5 (1) was synthesized by reacting a long-chain organic diamine N,N-dimethyl-1,3-propanediamine with SbBr3 as a metal halide precursor in HBr aqueous solution. Compound 1 possesses a one-dimensional chainlike structure with the second-harmonic generation switch and two continuous phase transitions above room temperature. The band gap of compound 1 is about 2.62 eV, exhibiting a semiconductive property, which may have important implications for the development of new optoelectronic devices.

The First Discovery of Spherical Carborane Molecular Ferroelectric Crystals.

Carborane compounds, known for their exceptional thermal stability and non-toxic attributes, have garnered widespread utility in medicine, supramolecular design, coordination/organometallic chemistry, and others. Although there is considerable interest among chemists, the integration of suitable carborane molecules into ferroelectric materials remains a formidable challenge. In this study, we employ the quasi-spherical design strategy to introduce functional groups at the boron vertices of the o-carborane cage, aiming to reduce molecular symmetry. This approach led to the successful synthesis of the pioneering ferroelectric crystals composed of cage-like carboranes: 9-OH-o-carborane (1) and 9-SH-o-carborane (2), which undergo above-room ferroelectric phase transitions (Tc) at approximately 367 K and 347 K. Interestingly, 1 and 2 represent uniaxial and multiaxial ferroelectrics respectively, with 2 exhibiting six polar axes and as many as twelve equivalent polarization directions. As the pioneering instance of carborane ferroelectric crystals, this study introduces a novel structural archetype for molecular ferroelectrics, thereby providing fresh insights into the exploration of molecular ferroelectric crystals with promising applications.

The hypothalamic steroidogenic pathway mediates susceptibility to inflammation-evoked depression in female mice.

BACKGROUND: Depression is two-to-three times more frequent among women. The hypothalamus, a sexually dimorphic area, has been implicated in the pathophysiology of depression. Neuroinflammation-induced hypothalamic dysfunction underlies behaviors associated with depression. The lipopolysaccharide (LPS)-induced mouse model of depression has been well-validated in numerous laboratories, including our own, and is widely used to investigate the relationship between neuroinflammation and depression. However, the sex-specific differences in metabolic alterations underlying depression-associated hypothalamic neuroinflammation remain unknown. METHODS: Here, we employed the LPS-induced mouse model of depression to investigate hypothalamic metabolic changes in both male and female mice using a metabolomics approach. Through bioinformatics analysis, we confirmed the molecular pathways and biological processes associated with the identified metabolites. Furthermore, we employed quantitative real-time PCR, enzyme-linked immunosorbent assay, western blotting, and pharmacological interventions to further elucidate the underlying mechanisms. RESULTS: A total of 124 and 61 differential metabolites (DMs) were detected in male and female mice with depressive-like behavior, respectively, compared to their respective sex-matched control groups. Moreover, a comparison between female and male model mice identified 37 DMs. We capitalized on biochemical clustering and functional enrichment analyses to define the major metabolic changes in these DMs. More than 55% of the DMs clustered into lipids and lipid-like molecules, and an imbalance in lipids metabolism was presented in the hypothalamus. Furthermore, steroidogenic pathway was confirmed as a potential sex-specific pathway in the hypothalamus of female mice with depression. Pregnenolone, an upstream component of the steroid hormone biosynthesis pathway, was downregulated in female mice with depressive-like phenotypes but not in males and had considerable relevance to depressive-like behaviors in females. Moreover, exogenous pregnenolone infusion reversed depressive-like behaviors in female mice with depression. The 5α-reductase type I (SRD5A1), a steroidogenic hub enzyme involved in pregnenolone metabolism, was increased in the hypothalamus of female mice with depression. Its inhibition increased hypothalamic pregnenolone levels and ameliorated depressive-like behaviors in female mice with depression. CONCLUSIONS: Our study findings demonstrate a marked sexual dimorphism at the metabolic level in depression, particularly in hypothalamic steroidogenic metabolism, identifying a potential sex-specific pathway in female mice with depressive-like behaviors.

Three-Dimensional Perovskite Phase Transition Materials with Switchable Second Harmonic Generation Properties Introduced by Homochiral (1S,4S)-2,5-Diazabicyclo[2.2.1]-heptane.

Switchable second harmonic generation (SHG) materials have potential applications in information storage, signal processing, and so on because they can switch between SHG-on and SHG-off states. In this work, we designed and synthesized three organic-inorganic hybrid Rb halide three-dimensional (3D) perovskite materials [1S,4S 2,5-2.2.1-H2dabch]RbX3·0.5H2O (X = Cl, 1; Br, 2; I, 3) based on the chiral 1S,4S-2,5-diazabicyclo[2.2.1]heptane (1S,4S-2,5-2.2.1-dabch). The selection of homochiral organic cations ensures that the compounds 1∼3 crystallize in the noncentrosymmetric and chiral space group P212121, which further leads to reversible SHG responses of the three compounds. Through differential scanning calorimetry (DSC) and dielectric measurements, it revealed that the phase transition point of the compounds 1∼3 increased with RbCl, RbBr, and RbI. This is because the hydrogen interaction H···X between the inorganic framework [RbX3]n and the organic cation [1S,4S-2,5-2.2.1-H2dabch]2+ is increased with the order of I > Br > Cl. This study can provide an effective molecular design strategy for the exploration and construction of temperature-tunable SHG switching materials.

Two 3D Rubidium Halide Organic-Inorganic Hybrid Perovskite Ferroelectrics Templated by Quasi-Spherical Organic Amine 1,4-Diazabicyclo[3.2.2]nonane.

The emergence of (CH3 NH3 )PbI3 has brought the development of three-dimensional (3D) organic-inorganic hybrid perovskite (OIHP) structures with ABX3 type to a higher level; however, most 3D frameworks are constructed by corner-sharing of BX6 octahedra. Herein, we substituted the spherical molecule 1,4-diazabicyclo[2.2.2]octane (2.2.2-dabco) with 1,4-diazabicyclo[3.2.2]nonane (1,4-3.2.2-dabcn) as a template to react with RbX (X=Br, I) in the corresponding HX acids under the consideration of reducing the molecular symmetry. Two 3D OIHP compounds [1,4-3.2.2-H2 dabcn]RbI3 ⋅H2 O (1) and [1,4-3.2.2-H2 dabcn]RbBr3 (2) crystallized in non-centrosymmetric point group mm2 before the phase transition point were isolated. Among them, the 3D inorganic framework of 1 is constructed by sharing the corner of [RbI6 ] octahedra, while that of 2 is constructed by sharing the corner and face of [RbBr6 ] octahedra to acquire large cavities to accommodate the organic amine cation [1,4-3.2.2-H2 dabcn]2+ ; this 3D framework type is unprecedented in the OIHPs. As expected, compounds 1 and 2 exhibit reversible phase transition, dielectric and second harmonic generation (SHG) and ferroelectric properties, in which the phase transition temperature of 2 at 374 K is much higher than compound 1 at 280 K.

3D Perovskite (1,5-3.2.2-H2dabcn)CsBr3 with Reverse Symmetry Breaking.

Even though hybrid organic-inorganic perovskites (HOIPs) have been studied by many scholars in recent years, there are not many reports on three-dimensional (3D) alkali metal cesium halide perovskites. Here, we report an unprecedented 3D HOIP molecule (1,5-3.2.2-H2dabcn)CsBr3 (1), in which the 3D anionic framework is constructed by corner-sharing CsBr6 octahedra and organic cations [1,5-3.2.2-H2dabcn]2+ are located in the cavities formed by the octahedra. Organic cations interact with an inorganic metal frame via two N-H···Br hydrogen bonds. Compound 1 undergoes a reversible order-disorder phase transition and exhibits switchable dielectric and second-harmonic generation (SHG) properties. Interestingly, product 1 crystallizes in a non-centrosymmetric space group Pmn21 at the low-temperature phase (LTP) and transforms into a centrosymmetric space group P2/m at the high-temperature phase (HTP). The space group Pmn21 in the LTP has a higher symmetry than P2/m in the HTP. This inverted symmetry breaking is very unusual.

Organic-Inorganic Hybrid Compound [H2-1,5-Diazabicyclo[3.3.0]octane]ZnBr4 with Reverse Symmetry Breaking Shows a Switchable Dielectric Anomaly and Robust Second Harmonic Generation Effect.

An organic-inorganic hybrid molecule [3.3.0-H2dabco]ZnBr4 (1) with switchable phase transition, dielectric anomaly, and second harmonic generation (SHG) effect was synthesized by reaction of 1,5-diazabicyclo[3.3.0]octane (3.3.0-dabco) with ZnBr2 in concentrated hydrobromic acid aqueous solution. Differential scanning calorimetry (DSC) and dielectric measurements revealed that 1 exhibits a reversible high-temperature phase transition, accompanied by a distinct step-like dielectric anomaly at 373 K. Exceptionally, the single crystal structure analysis at different temperatures revealed that 1 undergoes reverse symmetry breaking during the phase transition, in which the high-symmetry space group Cc in the low temperature phase (LTP) is transformed to the low-symmetry space group P1̅ in the high temperature phase (HTP). In addition, with the conversion from the non-centrosymmetric (NCS) to the centrosymmetric (CS) space group, the SHG of 1 can switch from SHG-ON to SHG-OFF for at least four cycles without obvious decay.

The Role of Fluorine-Substituted Positions on the Phase Transition in Organic-Inorganic Hybrid Perovskite Compounds.

Although research on organic-inorganic hybrid perovskites (OIHPs) has grown exponentially in the past two decades, the high phase transition temperature of OIHP materials is still one of the insurmountable difficulties. Herein, a series of A2BX4 type OIHP materials [(2,n-DFBA)2PbCl4] (n = 3, for 1; n = 4, for 2; n = 5, for 3; n = 6, for 4) have been prepared by reactions of double-substituted difluorobenzylamine (difluorobenzylamine = DFBA) with lead chloride in concentrated HCl aqueous solution. It was found the OIHP compounds 1-3 proceed a switchable phase transition with phase transition temperatures (Tc) at 449 K (1), 462 K (2) and 500 K (3), higher than that of the parent compound [(BA)2PbCl4] (BA = benzylammonium) at 438 K, but compound 4 exhibits no phase transition. A crystal structure analysis elucidated that the organic template ligands DFBA lead in the inorganic part in compounds 1-3 to a two-dimensional (2D) perovskite structure, while that in compound 4 leads to a one-dimensional (1D) chain structure. The different double-substituted positions of fluorine atoms on benzylamine have important influences on the phase transition in compounds 1-4.

Contribution of upregulated aminoacyl-tRNA biosynthesis to metabolic dysregulation in gastric cancer.

BACKGROUND AND AIM: Metabolic reprogramming is characterized by dysregulated levels of metabolites and metabolic enzymes. Integrated metabolomic and transcriptomic data analysis can help to elucidate changes in the levels of metabolites and metabolic enzymes, screen the core metabolic pathways, and develop novel therapeutic strategies for cancer. METHODS: Here, the metabolome of gastric cancer tissues was determined using liquid chromatography-mass spectrometry. The transcriptome data from The Cancer Genome Atlas dataset were integrated with the liquid chromatography-mass spectrometry data to identify the common dysregulated gastric cancer-specific metabolic pathways. Additionally, the protein expression and clinical significance of key metabolic enzymes were examined using a gastric cancer tissue array. RESULTS: Metabolomic analysis of 16 gastric cancer tissues revealed that among the 15 dysregulated metabolomic pathways, the aminoacyl-tRNA biosynthesis pathway in the gastric tissues was markedly upregulated relative to that in the adjacent noncancerous tissues, which was consistent with the results of transcriptome analysis. Bioinformatic analysis revealed that among the key regulators in the aminoacyl-tRNA biosynthesis pathway, the expression levels of threonyl-tRNA synthetase (TARS) and phenylalanyl-tRNA synthetase (FARSB) were correlated with tumor grade and poor survival, respectively. Additionally, gastric tissue array data analysis indicated that TARS and FARSB were upregulated in gastric cancer tissues and were correlated with poor prognosis and tumor metastasis. CONCLUSIONS: This study demonstrated that the aminoacyl-tRNA biosynthesis pathway is upregulated in gastric cancer and both TARS and FARSB play key roles in the progression of gastric cancer. Additionally, a novel therapeutic strategy for gastric cancer was proposed that involves targeting the aminoacyl-tRNA biosynthesis pathway.

Association between serum pepsinogen and atherosclerotic cardiovascular disease.

BACKGROUND AND AIM: Serum pepsinogens (PGs) are biomarkers for gastric mucosal damage and have been reported to be associated with atherosclerosis. Its correlation with atherosclerotic cardiovascular disease (ASCVD) is still unknown. This study aimed to explore the association between serum PGs and ASCVD for providing physicians with an integrative picture to make rational plans in the diagnosis and treatment of ASCVD. METHODS AND RESULTS: The concentrations of serum PGs and their distributions between ASCVD and non-ASCVD were compared by non-parametric test, Chi-squared test and Fisher exact test. The correlation between variables was analyzed by Spearman's correlation test. The association of serum PGs with ASCVD was analyzed by the binary logistic regression and two-piecewise linear regression. A total of 8355 recruited cases were eligible for the study. The concentrations of serum PGs were significantly different between the ASCVD and non-ASCVD groups (P = 0.025, P < 0.001). The lower PGI and PGR levels were significantly correlated with a high risk of ASCVD presence after adjustment for 26 potential covariates. Moreover, there was a linear relationship between the high level of PGII and the high risk of ASCVD [adjusted OR = 1.16 (1.00, 1.37), P = 0.07]. A nonlinear relationship of PGI/PGR and ASCVD (P = 0.08/<0.001) was also revealed. The risk of ASCVD increased with a range of log PGI ≥2.13 (PGI≥131 ng/mL) [adjusted OR = 4.67 (1.00, 23.17)], and decreased with a range of log PGR ≥0.22 (1.65) [adjusted OR = 0.59 (0.48, 0.74), P < 0.001]. CONCLUSIONS: Serum PGI and PGR are nonlinearly correlated with ASCVD, while PGII is linearly correlated with ASCVD. Among all PGs, PGR may serve as a reliable biomarker for ASCVD.

Rational Design of Ceramic-Like Molecular Ferroelectric by Quasi-Spherical Theory.

Molecular ferroelectrics are attracting tremendous interest because of their easy and environmentally friendly processing, light weight, low acoustical impedance, and mechanical flexibility, which are viable alternatives or supplements to conventional ceramic ferroelectrics. However, reports of ceramic-like molecular ferroelectrics that can be applied in the polycrystalline form have been scarce. Here, according to the "quasi-spherical theory", we successfully synthesized a ceramic-like molecular ferroelectric with an m3mFmm2 type phase transition at 357 K, 1,5-diazabicyclo[3.2.1]octonium tetrafluoroborate ([3.2.1-dabco]BF4), which can show excellent ferroelectric performance in the polycrystalline thin-film form at room temperature. On the basis of the reported molecular ferroelectric [2.2.2-dabco]BF4 (2.2.2-dabco = 1,4-diazabicyclo[2.2.2]octonium) with an Aizu notation of 4/mmmFmm2 and two polar axes, we changed the [2.2.2-dabco]+ cation to the [3.2.1-dabco]+ cation to reduce the molecular symmetry and keep the quasi-spherical shape simultaneously, making the number of polar axes up to six. Moreover, the spontaneous polarization Ps gets successfully increased from 4.9 µC cm-2 in [2.2.2-dabco]BF4 to 5.5 µC cm-2 in [3.2.1-dabco]BF4. This precise molecular design strategy offers an efficient pathway to design ceramic-like molecular ferroelectrics.

The role of non-coding RNA on macrophage modification in tuberculosis infection.

Tuberculosis (TB), a serious disease caused by Mycobacterium tuberculosis (Mtb), remains the world's top infectious killer. It is well-established that TB can circumvent the host's immune response for long-term survival. Macrophages serve as the major host cells for TB growth and persistence and their altered functions are critical for the response of the host defense against TB exposure (elimination, latency, reactivation, and bacillary dissemination). Noncoding RNAs are crucial posttranscriptional regulators of macrophage discrimination. Therefore, this review highlights the regulatory mechanism underlying the relationship between noncoding RNAs and macrophages in TB infection, which may facilitate the identification of potential therapeutic targets and effective diagnosis biomarkers for TB disease.

Magnetic targeting enhances the cutaneous wound healing effects of human mesenchymal stem cell-derived iron oxide exosomes.

Human mesenchymal stem cell (MSC)-derived exosomes (Exos) are a promising therapeutic agent for cell-free regenerative medicine. However, their poor organ-targeting ability and therapeutic efficacy have been found to critically limit their clinical applications. In the present study, we fabricated iron oxide nanoparticle (NP)-labeled exosomes (Exo + NPs) from NP-treated MSCs and evaluated their therapeutic efficacy in a clinically relevant model of skin injury. We found that the Exos could be readily internalized by human umbilical vein endothelial cells (HUVECs), and could significantly promote their proliferation, migration, and angiogenesis both in vitro and in vivo. Moreover, the protein expression of proliferative markers (Cyclin D1 and Cyclin A2), growth factors (VEGFA), and migration-related chemokines (CXCL12) was significantly upregulated after Exo treatment. Unlike the Exos prepared from untreated MSCs, the Exo + NPs contained NPs that acted as a magnet-guided navigation tool. The in vivo systemic injection of Exo + NPs with magnetic guidance significantly increased the number of Exo + NPs that accumulated at the injury site. Furthermore, these accumulated Exo + NPs significantly enhanced endothelial cell proliferation, migration, and angiogenic tubule formation in vivo; moreover, they reduced scar formation and increased CK19, PCNA, and collagen expression in vivo. Collectively, these findings confirm the development of therapeutically efficacious extracellular nanovesicles and demonstrate their feasibility in cutaneous wound repair.

Germline BRCA2 Truncating Mutation in Familial Esophageal Squamous Cell Carcinoma: A Case Controlled Study in China.

BACKGROUND Germline mutations of BRCA2 have been reported in various malignancies. We investigated BRCA2 germline mutations in familial clusters with esophageal squamous cell carcinoma (ESCC). MATERIAL AND METHODS We screened the DNA of familial ESCC patients for BRCA2 germline mutations with whole gene sequencing. Multiple BRCA2 mutations including one novel splice variant, c.426-2A>G were identified. Other family members, sporadic ESCC patients, and controls were also assessed for the novel mutation. RESULTS The mutation c.426-2A>G was found in 2 affected ESCC sisters and 7 other family members. The splice variant mutation results in exon 5 skipping with a frame shift leading to a premature stop codon in exon 6 and truncation. Novel mutation tracking ruled out single nucleotide polymorphism (SNP) in 100 chromosomes of healthy individuals. CONCLUSIONS BRCA2 germline mutation in ESCC patients may play a role in genetic susceptibility to familial ESCC. Genetic analysis of BRCA2 in patients with familial ESCC could provide opportunities for targeted therapies.

The meta-analysis for ideal cytokines to distinguish the latent and active TB infection.

BACKGROUND: One forth whole-world population is infected with Mycobacterium tuberculosis (Mtb), but 90% of them are asymptotic latent infection without any symptoms but positive result in IFN-γ release assay. There is lack of ideal strategy to distinguish active tuberculosis (TB) and latent tuberculosis infection (LTBI). Some scientist had focused on a set of cytokines as biomarkers besides interferon- gamma (IFN-γ) to distinguish active TB and LTBI, but with considerable variance of results. This meta-analysis aimed to evaluate the overall discriminative ability of potential immune molecules to distinguish active TB and LTBI. METHODS: PubMed, the Cochrane Library, and Web of Science databases were searched to identify studies assessing diagnostic roles of cytokines for distinguishing active TB and LTBI published up to August 2018. The quality of enrolled studies was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The pooled diagnostic sensitivity and specificity of each cytokine was calculated by using Meta-DiSc software. Area under the summary receiver operating characteristic curve (AUC) was used to summarize the overall diagnostic performance of each biomarker. RESULTS: Fourteen studies with 982 subjects met the inclusion criteria, including 526 active TB and 456 LTBI patients. Pooled sensitivity, specificity and AUC for discriminating between active TB and LTBI were analyzed for IL-2 (0.87, 0.61 and 0.9093), IP-10 (0.77, 0.73 and 0.8609), IL-5 (0.64, 0.75 and 0.8533), IL-13 (0.75, 0.71 and 0.8491), IFN-γ (0.67, 0.75 and 0.8031), IL-10 (0.68, 0.74 and 0.7957) and TNF-α (0.67, 0.64 and 0.7783). The heterogeneous subgroup analysis showed that cytokine detection assays, TB incidence, and stimulator with Mtb antigens are main influence factors for their diagnostic performance. CONCLUSIONS: The meta-analysis showed cytokine production could assist the distinction between active TB and LTBI, IL-2 with the highest overall accuracy. No single biomarker is likely to show sufficiently diagnostic performance due to limited sensitivity and specificity. Further prospective studies are needed to identify the optimal combination of biomarkers to enhanced diagnostic capacity in clinical practice.

Diagnostic accuracy of in-house real-time PCR assay for Mycobacterium tuberculosis: a systematic review and meta-analysis.

BACKGROUND: In recent years, studies on the diagnostic accuracy of in-house real-time PCR (hRT-PCR) assay for the detection of Mycobacterium tuberculosis (Mtb) have been reported with unignorable discrepancies. To assess the overall accuracy of the hRT-PCR assay for Mtb diagnosis in different samples for individuals with active pulmonary and extra-pulmonary Mtb infection, a systematic review and meta-analysis were performed. METHODS: The PUBMED, EMBASE, Web of Science, and Cochrane databases were searched up to June 2017 for eligible studies that estimated diagnostic sensitivity and specificity with the hRT-PCR assay in respiratory and non-respiratory samples in pulmonary and extra-pulmonary Mtb infection patients, with Mtb culture as the reference standard. Bivariate random effect models were used to provide pooled estimation of diagnostic accuracy. Further, subgroup and meta-regression analyses were performed to explore sources of heterogeneity. The risk of bias was assessed by the QUADAS-2 tool. RESULTS: Of the 3589 candidate studies, 18 eligible studies met our inclusion criteria. Compared to Mtb culture data, the pooled sensitivity and specificity were 0.96 and 0.92, respectively. The diagnostic odds ratio (DOR) was 192.96 (95% CI 68.46, 543.90), and the area under the summary ROC curve (AUC) was 0.9791. There was significant heterogeneity in sensitivity and specificity among the enrolled studies (p < 0.001). The studies with high-quality assessment and application of respiratory specimen were associated with better accuracy. CONCLUSIONS: In low-income/high-burden settings, our results suggested that the hRT-PCR assay could be a useful test for the diagnosis of TB with high sensitivity and specificity.

IL-10 Dampens the Th1 and Tc Activation through Modulating DC Functions in BCG Vaccination.

BCG, the only registered vaccine against Mycobacterial Tuberculosis (TB) infection, has been questioned for its protective efficacy for decades. Although lots of efforts were made to improve the BCG antigenicity, few studies were devoted to understand the role of host factors in the variability of the BCG protection. Using the IL-10KO mice and pulmonary tuberculosis infection model, we have addressed the role of IL-10 in the BCG vaccination efficacy. The data showed that IL-10-deficient dendritic cells (DCs) could promote the immune responses through upregulation of the surface costimulatory molecule expression and play an orchestra role through activating CD4+T cell. IL-10-deficient mice had higher IFN γ, TNF α, and IL-6 production after BCG vaccination, which was consistent with the higher proportion of IFN γ +CD3+, IFN γ +CD4+, and IFN γ +CD8+ T cells in the spleen. Particularly, the BCG-vaccinated IL-10KO mice showed less inflammation after TB challenge compared to WT mice, which was supported by the promoted Th1 and Tc, as well as the downregulated Treg responses in IL-10 deficiency. In a conclusion, we demonstrated the negative relationship between Th1/Tc responses with IL-10 production. IL-10 deficiency restored the type 1 immune response through DC activation, which provided better protection against TB infection. Hence, our study offers the first experimental evidence that, contrary to the modulation of BCG, host immunity plays a critical role in the BCG protective efficacy against TB.

Discovery of an Antiperovskite Ferroelectric in [(CH3)3NH]3(MnBr3)(MnBr4).

It is known that perovskites with the general chemical formula of ABX3 (A, B = cations, X = anion) have been intensively studied over the last half century because of their diverse functional properties, such as ferroelectricity in BaTiO3, piezoelectricity in PZT (lead zirconate titanate), and recently developed photovoltaic properties in CH3NH3PbI3. However, rather less attention has been paid to their "inverse" analogs, antiperovskites, which have a chemical formula X3BA, where A and B are anions and X is a cation. Although most of important ferroelectrics are perovskites, no antiperovskite ferroelectrics have been found since the discovery of antiperovskites in 1930. Here, for the first time, we report a X3BA antiperovskite ferroelectric [(CH3)3NH]3(MnBr3)(MnBr4) (where (CH3)3NH is X, MnBr3 is B, and MnBr4 is A), which shows outstanding ferroelectricity with a significantly high phase transition temperature of 458 K as well as fascinating photoluminescence properties with two intense emissions. This finding opens a new avenue to explore the golden area of antiperovskites for high-performance functional materials.