Rapid Construction of Double Crystalline Prussian Blue Analogue Hetero-Superstructure.

The controllable construction of complex metal-organic coordination polymers (CPs) merits untold scientific and technological potential, yet remains a grand challenge of one-step construction and modulating simultaneously valence states of metals and topological morphology. Here, a thiocyanuric acid (TCA)-triggered strategy is presented to one-step rapid synthesis a double-crystalline Prussian blue analogue hetero-superstructure (PBA-hs) that comprises a Co3[Fe(CN)6]2 cube overcoated with a KCo[Fe(CN)6] shell, followed by eight self-assembled small cubes on vertices. Unlike common directing surfactants, TCA not only acts as a trigger for the fast growth of KCo[Fe(CN)6] on the Co3[Fe(CN)6]2 phase resulting in a PBA-on-PBA hetero-superstructure, but also serves as a flange-like bridge between them. By combining experiments with simulations, a deprotonation-induced electron transfer (DIET) mechanism is proposed for formation of second phase in PBA-hs, differing from thermally and photo-induced electron transfer processes. To prove utility, the calcined PBA-hs exhibits enhanced oxygen evolution reaction performance. This work provides a new method to design of novel CPs for enriching chemistry and material science. This work offers a practical approach to design novel CPs for enriching chemistry and material science.

Role of Up-Regulated Transmembrane Channel-Like Protein 5 in Pancreatic Adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a malignant tumor responsible for a heavy disease burden. Previously, only one pan-cancer study of Transmembrane channel-like protein 5 (TMC5) showed that TMC5 was highly expressed in PAAD, but the results lacked comprehensive verification, and the mechanism of TMC5 in PAAD was still unclear. METHODS: For exploring the expression and clinical value of TMC5 in PAAD better, we adopted a comprehensive evaluation method, using internal immunohistochemistry (IHC) data combined with microarray and RNA-sequencing data collected from public databases. The single cell RNA-sequencing (scRNA-seq) data were exploited to explore the TMC5 expression in cell populations and intercellular communication. The potential mechanism of TMC5 in PAAD was analyzed from the aspects of immune infiltration, transcriptional regulation, function and pathway enrichment. RESULTS: Our IHC data includes 148 PAAD samples and 19 non-PAAD samples, along with the available microarray and RNA-sequencing data (1166 PAAD samples, 704 non-PAAD samples). The comprehensive evaluation results showed that TMC5 was evidently up-regulated in PAAD (SMD = 1.17). Further analysis showed that TMC5 was over-expressed in cancerous epithelial cells. Furthermore, TMC5 was up-regulated in more advanced tumor T and N stages. Interestingly, we found that STAT3 as an immune marker of Th17 cells was not only positively correlated with TMC5 and up-regulated in PAAD tissues, but also the major predicted TMC5 transcription regulator. Moreover, STAT3 was involved in cancer pathway of PAAD. CONCLUSION: Up-regulated TMC5 indicates advanced tumor stage in PAAD patients, and its role in promoting PAAD development may be regulated by STAT3.

Combined analysis of receptor expression reflects inter-and intra-tumor heterogeneity in HR+/HER2+ breast cancer.

BACKGROUND: Hormone receptor-positive and human epidermal growth factor receptor 2-positive (HR+/HER2+ breast cancer comprise approximately 5-10% of all invasive breast cancers. However, the lack of knowledge regarding the complexity of tumor heterogeneity in HR+/HER2+ disease remains a barrier to more accurate therapies. This study aimed to describe the tumor heterogeneity of HR+/HER2+ breast cancer and to establish a novel indicator to identify the HER2-enriched subtype in patients with HR+/HER2+ breast cancer. METHODS: First of all, a comprehensive analysis was performed on HR+/HER2+ breast cancer samples from the TCGA (n = 141) and METABRIC (n = 104) databases. We determined the distribution of PAM50 intrinsic subtypes within the two cohorts and compared the somatic mutational profile and RNA expression features between HER2-enriched and non-HER2-enriched subtypes. From this, we constructed a novel marker termed rH/E, which was calculated as ERBB2 expression quantity/(ESR1 expression quantity + 1). Secondly, we performed multiplex immunofluorescence (mIF) to evaluate HER2 and estrogen receptor (ER) expression simultaneously in the third cohort, enrolling 43 cases of early HR+/HER2+ breast cancer from Cancer Hospital, Chinese Academy of Medical Sciences (CAMS). When using mIF, rH/E was adjusted to prH/E, which was calculated as HER2-positive cells%/(ER-positive cells + 1)%. RESULTS: All four main intrinsic subtypes were identified in HR+/HER2+ breast cancer, of which the luminal B subtype was the most common, followed by the HER2-enriched and luminal A subtypes. Significantly increased TP53 and ERBB3 and decreased PIK3CA somatic mutation frequency were observed in the HER2-enriched subtype compared with the non-HER2-enriched subtype. In addition, the HER2-enriched subtype was characterized by significantly higher ERBB2 and lower ESR1 expression. We then constructed a marker termed rH/E to reflect the relative expression of ERBB2 to ESR1 in each patient. rH/E discriminates the HER2-enriched subtype from the better than the expression of ERBB2 or ESR1 alone. In the CAMS cohort, we observed four subtypes of tumor cells: ER+/HER2-, ER+/HER2+, ER-/HER2+, and ER-/HER2-. Tumor cell diversity was common, with 86% of patients having all four subtypes of tumor cells. Moreover, prH/E showed a significant prognostic association in the CAMS cohort. CONCLUSIONS: This study furthers our understanding of the complexity of tumor heterogeneity in HR+/HER2+ breast cancer, and suggests that the combined analysis of ERBB2 and ESR1 expression may contribute to identifying patients with specific subtypes in this population.

Regioselective super-assembly of Prussian blue analogue.

The construction of high-asymmetrical structures demonstrates significant potential in improving the functionality and distinctness of nanomaterials, but remains a considerable challenge. Herein, we develop a one-pot method to fabricate regioselective super-assembly of Prussian blue analogue (PBA) -- a PBA anisotropic structure (PBA-AS) decorated with epitaxial modules--using a step-by-step epitaxial growth on a rapidly self-assembled cubic substrate guided by thiocyanuric acid (TCA) molecules. The epitaxial growth units manifest as diverse geometric shapes, which are predominantly concentrated on the {100}, {111}, or {100}+{111} crystal plane of the cubic substrate. The crystal plane and morphology of epitaxial module can be regulated by changing the TCA concentration and reaction temperature, enabling a high level of controllability over specific assembly sites and structures. To illustrate the advantage of the asymmetrical structure, phosphated PBA-AS demonstrates improved performance in the oxygen evolution reaction compared to simple phosphated PBA nanocube. This method offers valuable insights for designing asymmetrical nanomaterials with intricate architectures and versatile functionalities.

Candidate membrane protein gene families related to chemoreception in a wood-boring beetle, Pharsalia antennata Gahan (Coleoptera: Cerambycidae).

The longhorned beetles are key players for the maintenance of biodiversity in the terrestrial ecosystem. As xylophagous cerambycid insects in Coleoptera, the beetles have evolved specialized olfactory and gustatory systems to recognize chemical cues in the surrounding habitats. Despite over 36,000 described species in the Cerambycidae family including a wood-boring pest Pharsalia antennata, only a limited number of them (<1 %) have been characterized regarding their chemical ecology at the molecular level. Here, we surveyed four membrane protein gene families in P. antennata related to chemoreception through transcriptomics, phylogenetics and expression profiling analyses. In total, 144 genes encoding 72 odorant receptors (ORs), 33 gustatory receptors (GRs), 23 ionotropic receptors (IRs), four sensory neuron membrane proteins (SNMPs) and 12 ionotropic glutamate receptors (iGluRs) were harvested from the transcriptome of multiple tissues including antennae and legs of both sexes. The lineage-specific expansion of PantORs possibly implied a diverse range of host plants in this beetle, supporting this correlation between the host range and olfactory receptor repertoire sizes across cerambycid species. Further phylogenetic analysis revealed that Group 2 was contributed mainly to the large OR gene repertoire in P. antennata, representing 18 genes in Group 2A and eight in Group 2B. On the other hand, some key chemosensory genes were identified by applying a phylogenetics approach, such as PantOR21 close to the 2-phenylethanol receptor in Megacyllene caryae, three carbon dioxide GRs and seven Antennal IRs (A-IRs) clades. We also determined sex- and tissue-specific expression profiles of 69 chemosensory genes, revealing the high expression of most PantORs in antennae. Noticeably, 10 sex-biased genes (six PantORs, three PantIRs and PantSNMP1a) were presented in antennae, five sex-biased PantGRs in legs and 39 sex-biased genes (15 PantORs, 13 PantGRs, eight PantIRs and three PantSNMPs) in abdomens. These findings have greatly enhanced our knowledge about the chemical ecology of P. antennata and identify candidate molecular targets for mediating smell and taste of this beetle.

Dipole Effect on Oxygen Evolution Reaction of 2D Janus Single-Atom Catalysts: A Case of Rh Anchored on the P6m2-NP Configurations.

Catalytic performance of single-atom catalysts (SACs) relies fundamentally on the electronic nature and local coordination environment of the active site. Here, based on a machine-learning (ML)-aided density functional theory (DFT) method, we reveal that the intrinsic dipole in Janus materials has a significant impact on the catalytic activity of SACs, using 2D γ-phosphorus carbide (γ-PC) as a model system. Specifically, a local dipole around the active site is a key degree to tune the catalytic activity and can be used as an important descriptor with a high feature importance of 17.1% in predicting the difference of adsorption free energy (ΔGO* - ΔGOH*) to assess the activity of the oxygen evolution reaction. As a result, the catalytic performance of SACs can be tuned by an intrinsic dipole, in stark contrast to those external stimuli strategies previously used. These results suggest that dipole engineering and the revolutionary DFT-ML hybrid scheme are novel approaches for designing high-performance catalysts.

Expression profile and functional characterization of odorant binding proteins in a forest pest, Dioryctria abietella (Lepidoptera: Pyralidae).

In the forest ecosystem dominated by the Pinaceae plants, this boring pest Dioryctria abietella is subject to a variety of odorants derived from host and nonhost plants, in which olfactory-related proteins enriched in antennae are key behavioral modulators for the orientation of feeding and ovipositing hosts. Here, we addressed the odorant binding protein (OBP) gene family in D. abietella. Expression profiles revealed that the majority of OBPs were abundantly expressed in the antennae at a female-biased level. A male-antenna-biased DabiPBP1 was a strong candidate for detecting type I and type II pheromones of D. abitella female moths. Using a prokaryotic expression system combined with affinity chromatography, we harvested two antenna-dominant DabiOBPs. In the ligand-binding assays, the two DabiOBPs exhibited different odorant response spectra, as DabiOBP17 was tuned to most odorants with higher affinities compared to DabiOBP4. Of these, DabiOBP4 could strongly bind syringaldehyde and citral (dissociation constants (Ki) < 14 µM). A floral volatile, benzyl benzoate (Ki = 4.72 ± 0.20 µM), was the best ligand for DabiOBP17. Remarkably, several green leaf volatiles were found to strongly interact with DabiOBP17 (Ki < 8.5 µM), including Z3-hexenyl acetate, E2-hexenol, Z2-hexenal and E2-hexenal that may mediate a repellent response to D. abietella. Structural analyses of ligands revealed that the binding of the two DabiOBPs to odorants was associated with carbon-chain lengths and functional groups. Molecular simulations identified several key residues involved in the interactions of DabiOBPs and ligands, suggesting specific binding mechanisms. This study highlights olfactory roles of two antennal DabiOBPs in D. abietella, helping the identification of potentially behavioral compounds for the population control of this pest.

Association between the XRCC3 polymorphisms and breast cancer risk: meta-analysis based on case-control studies.

The previous published data on the association between X-ray repair cross-complementing group 3 (XRCC3) T241M, A4541G, and A17893G polymorphisms and breast cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the association between breast cancer and XRCC3 T241M (21,910 cases and 23,961 controls), A4541G (9,633 cases and 10,994 controls), and A17893G polymorphisms (10,761 cases and 12,235 controls) in different inheritance models. When all the eligible studies were pooled into the meta-analysis of XRCC3 T241M polymorphism, significantly increased risk of breast cancer was observed in recessive model (odds' ratio [OR] = 1.10, 95% confidence interval [CI] = 1.04-1.16) and in additive model (OR = 1.10, 95% CI = 1.03-1.16). No significant association was found between A4541G polymorphism and breast cancer risk. When all the eligible studies were pooled into the meta-analysis of XRCC3 A17893G polymorphism, no significant association was found in any genetic model. Additionally, when one study was deleted in the sensitive analysis, the results of XRCC3 A17893G were changed in the additive model (OR = 0.90, 95% CI = 0.82-0.99) and dominant model (OR = 0.94, 95% CI = 0.89-0.99). In summary, this meta-analysis indicates that T241M polymorphism show an increased breast cancer risk and A17893G polymorphism may be associated with decreased breast cancer risk. A study with the larger sample size is needed to further evaluated gene-environment interaction on XRCC3 T241M, A4541G, and A17893G polymorphisms and breast cancer risk.

Prognostic values of B-lines combined with clinical congestion assessment at discharge in heart failure patients.

AIMS: We aim to investigate the additive effect of B-lines on lung ultrasound (LUS) for predicting outcome in patients with heart failure (HF) when combined with conventional assessment of clinical congestion. METHODS AND RESULTS: This study prospectively enrolled 117 hospitalized HF patients (61 ± 16 years, 70.1% males) who underwent congestion assessment by the 'wet/dry' status, clinical congestion score (CCS), and B-lines on LUS. The primary endpoint was all-cause mortality or hospitalization for HF during the 180-day follow-up after discharge. The 'Wet', CCS ≥ 3, and B-lines >5, indicators of congestion positive (+), were observed in 83.8%, 76.1%, and 70.1% of the patients on admission, respectively; and the numbers significantly decreased to 41.9%, 41.9%, and 35.9% at discharge, respectively. The agreement between the 'wet/dry' status and B-lines (58.1%) or between CCS and B-lines (56.4%) was moderate at discharge, in terms of both positive and both negative. By incorporating the B-lines with assessment of clinical congestion, the patients at discharge were divided into three phenotypes as clinical congestion (+), clinical congestion (-) with B-lines (+), and clinical congestion (-) with B-lines (-). The Kaplan-Meier analysis showed a better survival in the both (-) group ('wet/dry' with B-lines: Chi-square 10.591, P = 0.005; CCS with B-lines: χ2 6.239, P = 0.031). When the 'wet' patients (n = 49) being taken as the reference, the 'dry' patients with B-lines (+) (n = 21) had an identical risk of the composite endpoint (hazard ratio [HR] adjusted for clinical covariates 1.021, 95% confidence interval [CI] 0.480-2.134, P = 0.974), while the 'dry' patients with B-lines (-) (n = 47) had a lower risk (HR 0.264, 95% CI 0.113-0.617, P = 0.002). When the CCS (+) patients (n = 49) being regarded as the reference, similar results were obtained in the patients with CCS (-) but B-lines (+) (n = 22) (HR 1.348, 95% CI 0.627-2.896, P = 0.444) as well as in those with both CCS (-) and B-lines (-) (n = 46) (HR 0.447, 95% CI 0.202-0.992, P = 0.048). CONCLUSIONS: The combination of B-lines on LUS and conventional assessment helped to identify new phenotypes of congestion that aid in the risk stratification of discharged HF patients. Further investigation is warranted to determine whether this strategy could be adopted as a guide for decongestion therapy.

ARNI or ARB Treats Residual Left Ventricular Remodelling after Surgery for Valvular Regurgitation: ReReRe study protocol.

AIMS: Patients with persistent or de novo left ventricular (LV) dilation and/or reduced ejection fraction (EF) after correction for primary aortic (AR) or mitral (MR) regurgitation (i.e. residual LV remodelling) have not been well studied with regard to guideline-directed medical therapy after successful aetiology-reversing surgery. We aim to (i) compare the effectiveness of sacubitril/valsartan vs. valsartan in promoting LV reverse remodelling and (ii) explore the safety of medication withdrawal after LV recovery. METHODS AND RESULTS: The ReReRe study is a multicentre, randomized, open-label, parallel trial that consists of two consecutive parts. A total of 371 patients with an LV end-diastolic diameter (LVEDD) > 60 mm or LVEF < 50%, assessed by transthoracic echocardiography (TTE) 7-14 days after valve surgery for significant AR or primary MR will be enrolled. The 1st randomization into the sacubitril/valsartan or valsartan groups and structured follow-up (1, 3, 6, 9, and 12 months after randomization) will be conducted to observe the primary objective as the rate of complete recovery of LV remodelling (i.e. LVEDD < 55 mm and LVEF ≥ 60% by TTE at two consecutive visits). Those who have complete recovery of LV remodelling will be enrolled in Study Part 2; consequently, they will receive the 2nd randomization into the medication withdrawal or maintenance group and 6-monthly visits for the observation of the primary objective as the rate of LV remodelling relapse (LVEDD > 60 mm or LVEF < 50%). The secondary objectives include the rate of composite clinical outcomes and the degree of change in 6-min walk distance and Kansas City Cardiomyopathy Questionnaire scores. CONCLUSIONS: The ReReRe study will provide new evidence for the treatment of patients with residual LV remodelling after curable unloaded surgery, as well as the duration of treatment. The study results will fill the gap in identifying an appropriate medical therapy regimen for this group of patients and perhaps for those with reversible aetiologies of heart failure.

Sintilimab-Induced Myocarditis Overlapping Myositis in a Patient With Metastatic Thymoma: A Case Report.

Although immune checkpoint inhibitor (ICI)-related myocarditis has been widely discussed, a lot of gaps and challenges in its clinical course and rational intervention remain elusive. We present the case of a 33-year-old man with a history of metastatic thymoma who developed dyspnea and muscle weakness 1 month after the first dose of sintilimab. He was asymptomatic but found to have a mild elevation of troponin-T and a moderate increase of creatine kinase 20 days after the infusion. Although the scheduled second dose was deferred, he developed dyspnea, left bundle branch block, and left ventricular enlargement that is suggestive of Grade 3 ICI-related myocarditis, complicated with myositis/myasthenia gravis 10 days later. Fortunately, his response to intensive immunosuppressive therapy was good.

Several natural products isolated from a red alga Gracilaria lemaneiformis and its evaluation of antialgal activity against six common red tide microalgae.

The ethanol extracts of Gracilaria lemaneiformis that have inhibitory effects on Karenia mikimotoi and Skeletonema costatum were separated by liquid-liquid extraction using different polar solvents into five fractions with antialgal activities (petroleum ether, chloroform, ethyl acetate, n-butanol, and water-soluble fractions). These fractions were chromatographed on silica gel to give, after repeated preparative thin-layer chromatography (PTLC) purification processes, 1-ß-D-ribofuranosyluracil (1), 3-hydroxymethyl-pyrrolopiperazine-2,5-dione (2), benzene-1,2-propanoic acid (3), 1-O-palmitoyl-2-O-palmitoleoyl-3-O-ß-D-galactopyranosyl glycerol (4), 7-oxabicyclo[4.1.0]-heptan-3-ol (5), linoleic acid (6), 3,4-dimethoxy-6-(methoxymethyl)-tetrahydro-2H-pyran-2,5-diol (7), and 3,7,11,16-tetramethyl -2-heptadecen-1-ol (8). Five of them, natural products 1, 2, 5, 7, and 8, were isolated from Gracilaria lemaneiformis for the first time, and three natural products (3, 5, and 8) were isolated from marine macroalgae for the first time. Among them, natural products (1, 2, 3, 4, and 6) showed the most obvious inhibition activities to the growth of Karenia mikimotoi and Skeletonema costatum at the concentration of 80 µg/mL. Therefore, antialgal activities of these five natural products against Amphidinium carterae, Heterosigma akashiwo, Karenia mikimotoi, Phaeocystis globosa, Prorocentrum donghaiense, and Skeletonema costatum were further tested at different concentrations (0.4, 2, 10, and 50 µg/mL). This was the first report of antialgal activities of five natural products (1, 2, 3, 4, and 6) to these six red tide microalgae. They showed significantly selective antialgal activities against all tested red tide microalgae. At the concentration of 50 µg/mL, the growth of Amphidinium carterae, Heterosigma akashiwo, Karenia mikimotoi, and Phaeocystis globosa was obviously inhibited; for Karenia mikimotoi, natural products 1, 2, and 6 have significant antialgal activities; the growth inhibition of Skeletonema costatum that was exposed to natural products 1, 3, and 4 was remarkable. Furthermore, by analyzing and comparing EC50-96 h values, it has been determined that natural product 3 (natural product 4) showed the superior application potential than potassium dichromate and some reported natural products (such as gossonorol isolated from Porphyra yezoensis, trehalose purified from Ulva pertusa) as a characteristic antialgal agent against Amphidinium carterae (Phaeocystis globosa). In addition, natural products 1 and 3 also showed good superiority than some reported natural products in inhibiting Skeletonema costatum; however, it was a pity that they were inferior to potassium dichromate in the inhibiting this red tide microalgae. Taken together, it is not hard to conclude that Gracilaria lemaneiformis was a good source of natural products with antialgal activities against some red tide microalgae.

Effects of erector spinae plane block on postoperative pain and side-effects in adult patients underwent surgery: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Recently, the effects of erector spinae plane block on postoperative pain have become increasingly controversial. This meta-analysis compared the effects of ESP block versus placebo on postoperative analgesia and side effects to determine whether the new technique is a reliable alternative for pain management. METHODS: PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang Database were searched for clinical studies investigating the analgesic effect of ESP block versus placebo. The primary outcomes included the visual analogue scale (VAS) at rest and during movement, as well as the postoperative morphine consumption in 24 h, and the secondary outcome was the rate of postoperative nausea and vomiting (PONV). The choice of using the fixed or random-effects model depended on whether the heterogeneity tested by I2 statistic was more than 50%. Seeking sources of heterogeneity and exploring the effect of clinical details on the final result were performed by subgroup analysis. Additionally, the test for stability of the pooled result was realized by sensitivity analysis. Finally, we evaluated the quality of the evidence for the outcomes. STATA 13.0 software was selected as the main analysis software in the meta-analysis. RESULTS: Eighteen randomized controlled trials (RCTs) comprising 1041 patients were reviewed. This meta-analysis showed that ESP block could significantly reduce patients' pain scores at 1 h, 6 h, 12 h, and 24 h after surgery at rest or during movement; 24-h postoperative morphine consumption; and the incidence of PONV. CONCLUSIONS: ESP block as a novel technique exhibited superior postoperative analgesic effects, reducing the postoperative complications in spinal, thoracic, and abdominal surgeries during the early postoperative period. However, as a new nerve block technique, numerous large-sized RCTs are needed for further research.

Knockdown by shRNA identifies SLC44A5 as a potential therapeutic target in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has been ranked the second leading cause of cancer­associated mortality in China and the third leading cause of cancer­associated mortality worldwide. A number of previous studies investigating SLC44A5 have revealed important biological insight and disease­specific functions. Therefore, the present study investigated the expression of SLC44A5 in HCC tissues and cell lines, and assessed the effect of SLC44A5 on the viability, cell cycle, apoptosis and invasion of HCC cell lines. The mRNA expression of SLC44A5 in 35 HCC tissues was significantly higher compared with that in 35 normal tissues. The protein expression of SLC44A5 was notably high in MHCC­97H and SMMC­7721 cells compared with that in four other HCC cell lines. Knockdown of SLC44A5 using short hairpin RNA inhibited cell viability and arrested the cells in G1 of the cell cycle by reducing the expression of cell cycle markers, proliferating cell nuclear antigen and cyclin­dependent kinase 2 in MHCC­97H and SMMC­7721 cells. Furthermore, SLC44A5 knockdown cells also exhibited cell apoptosis by reducing the expression levels of apoptosis markers, caspase­3 and caspase­9 in MHCC­97H and SMMC­7721 cells, and suppressed invasion. The present results suggested that SLC44A5 is involved in HCC carcinogenesis and progression in HCC, indicating that SLC44A5 may be a molecular target in cancer therapy.