Whole-transcriptome sequencing of phagocytes reveals a ceRNA network contributing to natural resistance to tuberculosis infection.

Tuberculosis (TB) is a major fatal infectious disease globally, exhibiting high morbidity rates and impacting public health and other socio-economic factors. However, some individuals are resistant to TB infection and are referred to as "Resisters". Resisters remain uninfected even after exposure to high load of Mycobacterium tuberculosis (Mtb). To delineate this further, this study aimed to investigate the factors and mechanisms influencing the Mtb resistance phenotype. We assayed the phagocytic capacity of peripheral blood mononuclear cells (PBMCs) collected from Resisters, patients with latent TB infection (LTBI), and patients with active TB (ATB), following infection with fluorescent Mycobacterium bovis Bacillus Calmette-Guérin (BCG). Phagocytosis was stronger in PBMCs from ATB patients, and comparable in LTBI patients and Resisters. Subsequently, phagocytes were isolated and subjected to whole transcriptome sequencing and small RNA sequencing to analyze transcriptional expression profiles and identify potential targets associated with the resistance phenotype. The results revealed that a total of 277 mRNAs, 589 long non-coding RNAs, 523 circular RNAs, and 35 microRNAs were differentially expressed in Resisters and LTBI patients. Further, the endogenous competitive RNA (ceRNA) network was constructed from differentially expressed genes after screening. Bioinformatics, statistical analysis, and quantitative real-time polymerase chain reaction were used for the identification and validation of potential crucial targets in the ceRNA network. As a result, we obtained a ceRNA network that contributes to the resistance phenotype. TCONS_00034796-F3, ENST00000629441-DDX43, hsa-ATAD3A_0003-CYP17A1, and XR_932996.2-CERS1 may be crucial association pairs for resistance to TB infection. Overall, this study demonstrated that the phagocytic capacity of PBMCs was not a determinant of the resistance phenotype and that some non-coding RNAs could be involved in the natural resistance to TB infection through a ceRNA mechanism.

Suppressing Metal Nanoparticle Ablation with Double-Pulse Femtosecond Laser Sintering.

As a branch of laser powder bed fusion, selective laser sintering (SLS) with femtosecond (fs) lasers and metal nanoparticles (NPs) can achieve high precision and dense submicron features with reduced residual stress, due to the extremely short pulse duration. Successful sintering of metal NPs with fs laser is challenging due to the ablation caused by hot electron effects. In this study, a double-pulse sintering strategy with a pair of time-delayed fs-laser pulses is proposed for controlling the electron temperature while still maintaining a high enough lattice temperature. We demonstrate that when delay time is slightly longer than the electron-phonon coupling time of Cu NPs, the ablation area was drastically reduced and the power window for successful sintering was extended by about two times. Simultaneously, the heat-affected zone can be reduced by 66% (area). This new strategy can be adopted for all the SLS processes with fs laser and unlock the power of SLS with fs lasers for future applications.

Genetic factors associated with acquired phenotypic drug resistance and its compensatory evolution during tuberculosis treatment.

OBJECTIVES: We elucidated the factors, evolution, and compensation of antimicrobial resistance (AMR) in Mycobacterium tuberculosis (MTB) isolates under dual pressure from the intra-host environment and anti-tuberculosis (anti-TB) drugs. METHODS: This retrospective case-control study included 337 patients with pulmonary tuberculosis from 15 clinics in Tianjin, China, with phenotypic drug susceptibility testing results available for at least two time points between January 1, 2009 and December 31, 2016. Patients in the case group exhibited acquired AMR to isoniazid (INH) or rifampicin (RIF), while those in the control group lacked acquired AMR. The whole-genome sequencing (WGS) was conducted on 149 serial longitudinal MTB isolates from 46 patients who acquired or reversed phenotypic INH/RIF-resistance during treatment. The genetic basis, associated factors, and intra-host evolution of acquired phenotypic INH/RIF-resistance were elucidated using a combined analysis. RESULTS: Anti-TB interruption duration of ≥30 days showed association with acquired phenotypic INH/RIF resistance (aOR = 2·2, 95% CI, 1·0-5·1) and new rpoB mutations (p = 0·024). The MTB evolution was 1·2 (95% CI, 1·02-1·38) single nucleotide polymorphisms per genome per year under dual pressure from the intra-host environment and anti-TB drugs. AMR-associated mutations occurred before phenotypic AMR appearance in cases with acquired phenotypic INH (10 of 16) and RIF (9 of 22) resistances. DISCUSSION: Compensatory evolution may promote the fixation of INH/RIF-resistance mutations and affect phenotypic AMR. The TB treatment should be adjusted based on gene sequencing results, especially in persistent culture positivity during treatment, which highlights the clinical importance of WGS in identifying reinfection and AMR acquisition before phenotypic drug susceptibility testing.

EspB and HtpG interact with the type III-A CRISPR/Cas system of Mycobacterium tuberculosis.

Introduction: Mycobacterium tuberculosis (MTB) has a type III-A clustered regularly interspaced short palindromic repeat/CRISPR-associated protein (CRISPR/Cas) system consisting of a Csm1-5 and CRISPR RNA (crRNA) complex involved in the defense against invading nucleic acids. However, CRISPR/Cas system in the MTB still is clearly unknown and needs to be further explored. Methods: In our work, two non-Cas system proteins EspB and HtpG protein were found and identified by LC-MS/MS. The effect of EspB and HtpG on Type III-A CRISPR/Cas System of M. tuberculosis was examined by using Plasmid interference assay and Co-immunoprecipitation analyses. We explored that EspB could interact with the crRNA RNP complex, but HtpG could inhibit the accumulation of the MTB Csm proteins and defense the mechanism of CRISPR/Cas system. Results: The proteins ESAT-6 secretion system-1(Esx-1) secreted protein B (EspB) and high-temperature protein G (HtpG), which were not previously associated with CRISPR/Cas systems, are involved in mycobacterial CRISPR/Cas systems with distinct functions. Conclusion: EspB is a novel crRNA-binding protein that interacts directly with the MTB crRNP complex. Meanwhile, HtpG influences the accumulation of MTB Csm proteins and EspB and interferes with the defense mechanism of the crRNP complex against foreign DNA in vivo. Thereby, our study not only leads to developing more precise clinical diagnostic tool to quickly detect for MTB infection, but also knows these proteins merits for TB biomarkers/vaccine candidates.

Novel serological biomarker panel using protein microarray can distinguish active TB from latent TB infection.

BACKGROUND: Rapid laboratory technologies which can effectively distinguish active tuberculosis (ATB) from controls and latent tuberculosis infection (LTBI) are lacked.The objective of this study is to explore MTB biomarkers in serum that can distinguish ATB from LTBI. METHODS: We constructed a tuberculosis protein microarray containing 64 MTB associated antigens. We then used this microarray to screen 180 serum samples, from patients with ATB and LTBI, and healthy volunteer controls. Both SAM (Significance analysis of microarrays) and ROC curve analysis were used to identify the differentially recognized biomarkers between groups. Extra 300 serum samples from patients with ATB and LTBI, and healthy volunteer controls were employed to validate the identified biomarkers using ELISA-based method. RESULTS: According to the results, the best biomarker combinations of 4 proteins (Rv1860, RV3881c, Rv2031c and Rv3803c) were selected. The biomarker panel containing these 4 proteins has reached a sensitivity of 93.3% and specificity of 97.7% for distinguishing ATB from LTBI, and a sensitivity of 86% and specificity of 97.6% for distinguishing ATB from HC. CONCLUSION: The biomarker combination in this study has high sensitivity and specificity in distinguishing ATB from LTBI, suggesting it is worthy for further validation in more clinical samples.

Plasma proteomic and metabolomic characterization of COVID-19 survivors 6 months after discharge.

Coronavirus disease 2019 (COVID-19) has gained prominence as a global pandemic. Studies have suggested that systemic alterations persist in a considerable proportion of COVID-19 patients after hospital discharge. We used proteomic and metabolomic approaches to analyze plasma samples obtained from 30 healthy subjects and 54 COVID-19 survivors 6 months after discharge from the hospital, including 30 non-severe and 24 severe patients. Through this analysis, we identified 1019 proteins and 1091 metabolites. The differentially expressed proteins and metabolites were then subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Among the patients evaluated, 41% of COVID-19 survivors reported at least one clinical symptom and 26.5% showed lung imaging abnormalities at 6 months after discharge. Plasma proteomics and metabolomics analysis showed that COVID-19 survivors differed from healthy control subjects in terms of the extracellular matrix, immune response, and hemostasis pathways. COVID-19 survivors also exhibited abnormal lipid metabolism, disordered immune response, and changes in pulmonary fibrosis-related proteins. COVID-19 survivors show persistent proteomic and metabolomic abnormalities 6 months after discharge from the hospital. Hence, the recovery period for COVID-19 survivors may be longer.

Cortactin and HER2 as potential markers for dural-targeted therapy in advanced gastric cancer.

To study the role of HER2/cortactin co-overexpression in advanced gastric cancer (GC). This study retrospectively enrolled 246 patients with stage III GC from January 2015 to December 2016 at our hospital. We explored, using immunostaining techniques, the role of the expression of cortactin and HER2 in the progression of advanced GC. The patient data, including age, sex, cortactin and HER2 expression, pathological parameters and survival, were collected. Univariate and multivariate analyses were used to analyze the characteristics, survival, and prognostic factors of the patients. The results showed that the expression of cortactin was significantly associated with vascular-lymphatic invasion (P < 0.001), N stage (P = 0.001), and TNM stage (P = 0.046). HER2 overexpression correlated with tumor size (P = 0.002), neural invasion (P = 0.002), Lauren classification (P = 0.005) and N stage (P = 0.034). Through univariate analysis using the Kaplan-Meier method, vascular-lymphatic invasion (P = 0.015), neural invasion (P = 0.021), N stage (P < 0.003), and HER2/cortactin co-overexpression (P < 0.028) were shown to be significantly associated with overall survival. Multivariate analysis demonstrated that vascular lymphatic invasion (hazard ratio = 1.481, 95% CI, 1.064 to 2.061, P = 0.020), neural invasion (hazard ratio = 1.505, 95% CI, 1.084 to 2.089, P = 0.015), N stage (N2/N1: hazard ratio = 1.655, 95% CI, 1.048 to 2.641, P < 0.031, N3/N1: hazard ratio = 2.089, 95% CI, 1.325 to 3.295, P < 0.002), and HER2/cortactin co-overexpression (hazard ratio = 1.427, 95% CI, 1.007 to 2.024, P = 0.046) were independent prognostic factors for poor overall survival. The results suggested that HER2/cortactin co-overexpression is an important predictive biomarker for GC patients. GC patients with HER2/cortactin co-overexpression may receive dual-targeted therapy to improve survival prognosis in the future.

Transcriptome analysis of the impact of diabetes as a comorbidity on tuberculosis.

BACKGROUND: Diabetes mellitus patients with pulmonary tuberculosis (DMTB) comorbidity has been recognized as a major obstacle towards achieving the World Health Organization goal of reducing the tuberculosis incidence rate by 90% in 2035. Host immune responses affected by diabetes can lead to increased susceptibility, severity and poor treatment outcomes in DMTB patients, and the underlying mechanisms have not yet been fully elucidated. This study aimed to identify key immunological and cellular components that contribute to increased morbidity and mortality in DMTB cases. METHODS: We performed RNA-Seq of total RNA isolated from peripheral blood mononuclear cells from 3 TB, 3 diabetes mellitus, and 3 DMTB patients and healthy controls, and analyzed differential expression, pathway enrichment and clustering of differentially-expressed genes (DEGs) to identify biological pathways altered specifically in DMTB patients. RESULTS: Bioinformatic analysis of DEGs suggested that enhanced inflammatory responses, small GTPases, the protein kinase C signaling pathway, hemostasis and the cell cycle pathway are likely implicated in the pathogenesis of the DMTB comorbidity. CONCLUSION: The DMTB comorbidity is associated with an altered transcriptome and changes in various biological pathways. Our study provides new insights on the pathological mechanism that may aid the development of host-directed therapies for this increasingly prevalent disease in high TB burden countries.

Efficacy of Dual-Targeting Combined Anti-Tuberculosis Drug Delivery System in the Treatment of Tuberculous Meningitis.

Tuberculous meningitis (TBM) is an incurable disease with high mortality. It is an extrapulmonary tuberculosis caused by mycobacterium tuberculosis which penetrated the blood-brain barrier and infected the meninges. Mycobacterium tuberculosis lurking in the body mainly reside in macrophages. Anti-tuberculous drugs usually can not target the blood-brain barrier and macrophages, the drug concentration in the lesion is low, which cannot effectively kill mycobacterium tuberculosis, making TBM difficult to treat. Targeted drug delivery systems can target drugs to specific nidus. In the study, we constructed a drug delivery system, which was a cell penetrate peptide B6 and phosphatidylserine (PS) modified polyethylene glycol (PEG) nanomaterial to target the blood-brain barrier and to target macrophages. This nanomaterial was a combined anti-tuberculosis drug delivery system encapsulating antituberculosis drugs rifampicin and pyrazinamide, designed to target macrophages in the brain and kill mycobacterium tuberculosis lurking in the macrophages. We have physically characterized the drug delivery system, and verified the bactericidal ability at cellular and animal level. Results have shown that the targeted drug delivery system had a remarkable efficacy to treat TBM in mice.

Transient Hydrodynamic Lattice Cooling by Picosecond Laser Irradiation of Graphite.

Recent theories and experiments have suggested hydrodynamic phonon transport features in graphite at unusually high temperatures. Here, we report a picosecond pump-probe thermal reflectance measurement of heat-pulse propagation in graphite. The measurement results reveal transient lattice cooling near the adiabatic center of a 15-µm-diameter ring-shape pump beam at temperatures between 80 and 120 K. While such lattice cooling has not been reported in recent diffraction measurements of second sound in graphite, the observation here is consistent with both hydrodynamic phonon transport theory and prior heat-pulse measurements of second sound in bulk sodium fluoride.

Judicious use of low-dosage corticosteroids for non-severe COVID-19: A case report.

Inflammation-mediated lung injury in severe cases of infection with SARS-CoV-2, the aetiological agent of Coronavirus disease 2019 (COVID-19), can lead to respiratory failure and death, and therapies that block or ameliorate lung injury-associated inflammatory "cytokine storms" and progression to acute respiratory distress syndrome (ARDS) are urgently needed. Therapeutic use of corticosteroids for this purpose has been controversial because of conflicting reports on their efficacy and immunosuppressive behaviour. The WHO has strongly recommended treating critical COVID-19 patients with systemic corticosteroid therapy, but recommends against corticosteroid therapy in non-severe COVID-19 disease because of a lack of strong evidence on its efficacy. This retrospective case report describing the successful treatment of a non-severe COVID-19 case in Changchun, China, by judicious administration of corticosteroids using a personalized therapeutic approach was recorded to strengthen the evidence base showing how corticosteroid use in non-severe COVID-19 cases can be safe and efficacious. Alongside supportive care and lopinavir/ritonavir antiviral drugs, a low dosage of methylprednisolone was administered over a short period to attenuate lung inflammation. Regular chest CT scans guided dosage reduction in response to lesion absorption and improved lung condition. Judicious use of corticosteroids safely attenuated disease progression and facilitated rapid and complete recovery.

Moiré Patterns in 2D Materials: A Review.

Quantum materials have attracted much attention in recent years due to their exotic and incredible properties. Among them, van der Waals materials stand out due to their weak interlayer coupling, providing easy access to manipulating electrical and optical properties. Many fascinating electrical, optical, and magnetic properties have been reported in the moiré superlattices, such as unconventional superconductivity, photonic dispersion engineering, and ferromagnetism. In this review, we summarize the methods to prepare moiré superlattices in the van der Waals materials and focus on the current discoveries of moiré pattern-modified electrical properties, recent findings of atomic reconstruction, as well as some possible future directions in this field.

Systematic Evaluation of Mycobacterium tuberculosis Proteins for Antigenic Properties Identifies Rv1485 and Rv1705c as Potential Protective Subunit Vaccine Candidates.

The lack of efficacious vaccines against Mycobacterium tuberculosis (MTB) infection is a limiting factor in the prevention and control of tuberculosis (TB), the leading cause of death from an infectious agent. Improvement or replacement of the BCG vaccine with one that reliably protects all age groups is urgent. Concerns exist that antigens currently being evaluated are too homogeneous. To identify new protective antigens, we screened 1,781 proteins from a high-throughput proteome-wide protein purification study for antigenic activity. Forty-nine antigens (34 previously unreported) induced antigen-specific gamma interferon (IFN-γ) release from peripheral blood mononuclear cells (PBMCs) derived from 4,452 TB and suspected TB patients and 167 healthy donors. Three (Rv1485, Rv1705c, and Rv1802) of the 20 antigens evaluated in a BALB/c mouse challenge model showed protective efficacy, reducing lung CFU counts by 66.2%, 75.8%, and 60%, respectively. Evaluation of IgG2a/IgG1 ratios and cytokine release indicated that Rv1485 and Rv1705c induce a protective Th1 immune response. Epitope analysis of PE/PPE protein Rv1705c, the strongest candidate, identified a dominant epitope in its extreme N-terminal domain accounting for 90% of its immune response. Systematic preclinical assessment of antigens Rv1485 and Rv1705c is warranted.

Vibrational spectral and structural characterization of multicomponent ternary co-crystal formation within acetazolamide, nicotinamide and 2-pyridone.

Ternary co-crystal, as a novel co-crystal design strategy developed on the basis of binary co-crystal, could be used to improve the physicochemical properties of active pharmaceutical ingredients (APIs) efficiently. However, it is difficult to obtain specific ternary co-crystals since such ternary one involves complex assembly of three different molecules. There are few reports on the micro-molecular structure respect of specific ternary co-crystal systems. In present work, 1:1:1 ternary co-crystal between acetazolamide (ACZ), nicotinamide (NAM) and 2-pyridone (2HP) has been synthesized successfully by mechanical grinding approach, and their structures are investigated by terahertz time-domain spectroscopy (THz-TDS) and Raman spectroscopy combined with theoretical calculation at the molecular level. The experimental THz spectral results showed that ACZ-NAM-2HP ternary co-crystal and the starting parent materials exhibited a few distinct spectral features in frequency-domain absorption spectra. Likewise, the Raman spectral result also shows some difference between the co-crystal and starting raw materials. Through density functional theory (DFT) calculations, the theoretical THz/Raman spectra and vibrational modes of two kind of possible ternary co-crystal theoretical forms (form I and II) between ACZ, NAM and 2HP were obtained. By comparing experimental and theoretical spectral results, the most suitable structure and vibrational modes of ACZ-NAM-2HP ternary co-crystal were determined. These results provide a wealth of information and unique method for studying molecular assembly and also inter-molecular interactions in specific ternary co-crystals at the molecular level in the emerging pharmaceutical co-crystal fields.

Clinical Value of Prognostic Nutritional Index in Prediction of the Presence and Severity of Neonatal Sepsis.

PURPOSE: The prognostic nutritional index (PNI) is a common indicator of nutritional and inflammatory status and is associated with various diseases such as cancer, cardiovascular diseases and infectious diseases. However, to date, no study has concentrated on the role of PNI in assessing and predicting the presence and severity of neonatal sepsis. Therefore, the present study aimed to explore the association of the PNI with the presence and severity of neonatal sepsis. MATERIALS AND METHODS: A total of 1196 neonates with suspected sepsis were enrolled in this study and their complete clinical and laboratory data were collected. PNI was calculated as serum albumin (g/L) + 5 × total lymphocyte count (109/L). Multivariate logistic regression analysis was performed to identify the risk factors for the presence and severity of neonatal sepsis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive value of PNI. All statistical analyses were performed using the statistical package SPSS 24.0. RESULTS: PNI was lower in neonates with sepsis and decreased significantly with the severity of sepsis. The correlation analysis demonstrated that the PNI was negatively correlated with the levels of the inflammatory marker procalcitonin (PCT) and C-reactive protein (CRP), and the length of hospital stay. Multivariate logistic regression analysis revealed that the PNI was independently and inversely associated with the presence and severity of neonatal sepsis. The area under the ROC curve of the PNI was 0.64 (95% confidence interval (CI): 0.61-0.67, P < 0.001) for severe sepsis and 0.69 (95% CI: 0.60-0.78, P < 0.001) for septic shock. In addition, our data revealed that PNI was also independently correlated with the length of hospital stay. CONCLUSION: PNI is an independent predictor for the presence and severity of neonatal sepsis.

Pressure-Dependent Behavior of Defect-Modulated Band Structure in Boron Arsenide.

The recent observation of unusually high thermal conductivity exceeding 1000 W m-1 K-1 in single-crystal boron arsenide (BAs) has led to interest in the potential application of this semiconductor for thermal management. Although both the electron/hole high mobilities have been calculated for BAs, there is a lack of experimental investigation of its electronic properties. Here, a photoluminescence (PL) measurement of single-crystal BAs at different temperatures and pressures is reported. The measurements reveal an indirect bandgap and two donor-acceptor pair (DAP) recombination transitions. Based on first-principles calculations and time-of-flight secondary-ion mass spectrometry results, the two DAP transitions are confirmed to originate from Si and C impurities occupying shallow energy levels in the bandgap. High-pressure PL spectra show that the donor level with respect to the conduction band minimum shrinks with increasing pressure, which affects the release of free carriers from defect states. These findings suggest the possibility of strain engineering of the transport properties of BAs for application in electronic devices.

Stacking-Order-Driven Optical Properties and Carrier Dynamics in ReS2.

Two distinct stacking orders in ReS2 are identified without ambiguity and their influence on vibrational, optical properties and carrier dynamics are investigated. With atomic resolution scanning transmission electron microscopy (STEM), two stacking orders are determined as AA stacking with negligible displacement across layers, and AB stacking with about a one-unit cell displacement along the a axis. First-principles calculations confirm that these two stacking orders correspond to two local energy minima. Raman spectra inform a consistent difference of modes I & III, about 13 cm-1 for AA stacking, and 20 cm-1 for AB stacking, making a simple tool for determining the stacking orders in ReS2 . Polarized photoluminescence (PL) reveals that AB stacking possesses blueshifted PL peak positions, and broader peak widths, compared with AA stacking, indicating stronger interlayer interaction. Transient transmission measured with femtosecond pump-probe spectroscopy suggests exciton dynamics being more anisotropic in AB stacking, where excited state absorption related to Exc. III mode disappears when probe polarization aligns perpendicular to b axis. The findings underscore the stacking-order driven optical properties and carrier dynamics of ReS2 , mediate many seemingly contradictory results in the literature, and open up an opportunity to engineer electronic devices with new functionalities by manipulating the stacking order.

Solid phase drug-drug pharmaceutical co-crystal formed between pyrazinamide and diflunisal: Structural characterization based on terahertz/Raman spectroscopy combining with DFT calculation.

Both pretty low solubility and high membrane permeability of diflunisal (DIF) would affect significantly its oral bioavailability as a typical non-steroidal anti-inflammatory substance. Meanwhile, pyrazinamide (PZA), known as one kind of important anti-tuberculosis drugs, has also several certain side effects. These deficiencies affect the large-scale clinical use of such drugs. Solid-state pharmaceutical co-crystallization is of contemporary interest since it offers an easy and efficient way to produce prospective materials with tunable improved properties. In the current work, a novel solid phase drug-drug co-crystal involving DIF and PZA with molar ratio 1:1 was prepared through the mechanical grinding approach, and vibrational spectroscopic techniques including terahertz time-domain spectroscopy (THz-TDS) and Raman spectroscopy were performed to identify DIF, PZA and their pharmaceutical drug-drug co-crystal. The absorption peaks observed in the THz spectra of the co-crystal were at 0.35, 0.65, 1.17, 1.31 and 1.42 THz respectively, which are obviously different from parent materials. Similarly, Raman spectra could also be used to characterize the difference shown between the co-crystal and parent compounds. Structures and vibrational patterns of three kinds of possible co-crystal theoretical forms (form I, II and III) between DIF and PZA have been simulated by performing density functional theory (DFT) calculations. Theoretical results and THz/Raman vibrational spectra of DIF-PZA co-crystal show that the DIF links to PZA via the carboxylic acid-pyridine hetero-synthon association establishing the theoretical form I, which is a much-higher degree of agreement with experimental results than those of other two co-crystal forms. These results provide us a unique method for characterizing the composition of co-crystal structures, and also provide a wealth of drug-drug co-crystal structural information for improving physicochemical properties and pharmacological activities of specific drugs at the molecular-level.

Structural insights into anhydrous and monohydrated forms of 2,4,6-trihydroxybenzoic acid based on Raman and terahertz spectroscopic characterization.

In order to characterize molecular structures of 2,4,6-trihydroxybenzoic acid (PCA) by means of vibrational spectroscopic techniques, we report investigation of PCA monohydrated form and its anhydrous polymorphic one by using terahertz and Raman spectral characterization. The experimental THz spectra show that the monohydrated PCA only has two absorption bands at 0.69 and 1.65 THz respectively in the frequency region from 0.2 to 1.8 THz, meanwhile the anhydrous form has a few significantly different absorption bands at 0.75, 1.01, 1.46 and 1.64 THz, respectively. Furthermore, Raman spectra characterized such differences of vibrational modes shown within 200-1800 cm-1 region about the monohydrated and anhydrous forms of PCA. In view of various possible theoretical structural forms that may exist in anhydrous PCA and its monohydrated one, density functional theory calculations were performed to simulate optimized structures and vibrational mode of above two PCA polymorphic forms. Theoretical results and experimental THz/Raman spectra of anhydrous PCA show that the dimer synthon via the carboxylic group ••• carboxyl group and its ortho-phenolic hydroxyl group inter-molecular hydrogen bonding interaction establishing the theoretical form I (AH-I) is more consistent with experimental observation than other theoretical forms (AH-II and AH-III). Meanwhile, the theoretical monohydrated form I (MH-I), which is formed by the linkage of carboxyl group and its ortho-phenolic hydroxyl group with water molecule, is also much more agreement with experimental spectral observations of PCA monohydrate than other monohydrated forms (MH-II and MH-III). Our study demonstrates effectively qualitative analysis of both micro-molecular structures and dehydrated transitions between anhydrous and hydrated polymorphic forms of PCA, thus providing rich information on the corresponding structural changes of anhydrous and hydrated PCAs due to various inter-molecular and intra-molecular interactions based on their finger-print vibrational spectra combined with theoretical simulations.

Synthesis of clathrate cerium superhydride CeH9 at 80-100 GPa with atomic hydrogen sublattice.

Hydrogen-rich superhydrides are believed to be very promising high-Tc superconductors. Recent experiments discovered superhydrides at very high pressures, e.g. FeH5 at 130 GPa and LaH10 at 170 GPa. With the motivation of discovering new hydrogen-rich high-Tc superconductors at lowest possible pressure, here we report the prediction and experimental synthesis of cerium superhydride CeH9 at 80-100 GPa in the laser-heated diamond anvil cell coupled with synchrotron X-ray diffraction. Ab initio calculations were carried out to evaluate the detailed chemistry of the Ce-H system and to understand the structure, stability and superconductivity of CeH9. CeH9 crystallizes in a P63/mmc clathrate structure with a very dense 3-dimensional atomic hydrogen sublattice at 100 GPa. These findings shed a significant light on the search for superhydrides in close similarity with atomic hydrogen within a feasible pressure range. Discovery of superhydride CeH9 provides a practical platform to further investigate and understand conventional superconductivity in hydrogen rich superhydrides.