Theoretical Insights into Regulation of Red/Blue-Shifting Hydrogen Bonds Through Cooperativity with Regium Bonds.

To deeply understand the characteristics and regulation of red/blue-shifting hydrogen bonds (HBs), a theoretical investigation was conducted to explore the cooperativity between regium bonds and HBs in the complexes of Y···MCN···HCX3 (M = Cu, Ag, Au; Y = H2O, HCN, NH3; X = F, Cl). When MCN formed a hydrogen bonding dimer with CHF3 or CHCl3, the blue shift of C-H vibration frequency v(C-H) decreases as the following sequence Au > Cu > Ag, and the red shift decreases following the order Ag > Cu > Au. Upon the formation of ternary complexes, the presence of regium bonding interactions exerts a positive synergistic effect, resulting in the strengthening of the HBs. This, in turn, leads to noticeable changes in the red and blue shifts of v(C-H). In CHF3 complexes, v(C-H) undergoes a decrease in the blue shift, whereas that in CHCl3 exhibits an increase in the red shift. Especially, a transition from blue to red shift is observed within the AuCN···HCCl3 complex. As the strength of the regium bond increases, the trend of shifting from blue to red becomes more pronounced. For a given MCN, the changes occur in the order of NH3 > HCN > H2O. The interplay between two interactions was revealed by the molecular electrostatic potentials (MEP), the atoms in the molecule (AIM), and natural bond orbitals (NBO) analysis. It is revealed that Δv(C-H) is linearly correlated with a series of configuration and energy parameters. We explain the red- and blue-shifting HBs and their changes from the perspective of hyperconjugation and rehybridization. The presence of the positive synergistic effect enhances the hyperconjugation effect, thereby leading to a reduction in the blue shift and an increase in the red shift of v(C-H) within the complexes. This study enriches previous mechanisms regarding red- and blue-shifting HBs and introduces a novel idea to manipulate the characteristics of HBs, with the potential to impact the functioning of intricate systems.

Perineural Invasion in Cervical Cancer: A Hidden Trail for Metastasis.

Perineural invasion (PNI), the neoplastic invasion of nerves, is an often overlooked pathological phenomenon in cervical cancer that is associated with poor clinical outcomes. The occurrence of PNI in cervical cancer patients has limited the promotion of Type C1 surgery. Preoperative prediction of the PNI can help identify suitable patients for Type C1 surgery. However, there is a lack of appropriate preoperative diagnostic methods for PNI, and its pathogenesis remains largely unknown. Here, we dissect the neural innervation of the cervix, analyze the molecular mechanisms underlying the occurrence of PNI, and explore suitable preoperative diagnostic methods for PNI to advance the identification and treatment of this ominous cancer phenotype.

Cerebrospinal Fluid Proteomics Identifies Potential Biomarkers for Early-Onset Alzheimer's Disease.

Background: Early-onset Alzheimer's disease (EOAD) exhibits a notable degree of heterogeneity as compared to late-onset Alzheimer's disease (LOAD). The proteins and pathways contributing to the pathophysiology of EOAD still need to be completed and elucidated. Objective: Using correlation network analysis and machine learning to analyze cerebrospinal fluid (CSF) proteomics data to identify potential biomarkers and pathways associated with EOAD. Methods: We employed mass spectrometry to conduct CSF proteomic analysis using the data-independent acquisition method in a Chinese cohort of 139 CSF samples, including 40 individuals with normal cognition (CN), 61 patients with EOAD, and 38 patients with LOAD. Correlation network analysis of differentially expressed proteins was performed to identify EOAD-associated pathways. Machine learning assisted in identifying crucial proteins differentiating EOAD. We validated the results in an Western cohort and examined the proteins expression by enzyme-linked immunosorbent assay (ELISA) in additional 9 EOAD, 9 LOAD, and 9 CN samples from our cohort. Results: We quantified 2,168 CSF proteins. Following adjustment for age and sex, EOAD exhibited a significantly greater number of differentially expressed proteins than LOAD compared to CN. Additionally, our data indicates that EOAD may exhibit more pronounced synaptic dysfunction than LOAD. Three potential biomarkers for EOAD were identified: SH3BGRL3, LRP8, and LY6 H, of which SH3BGRL3 also accurately classified EOAD in the Western cohort. LY6 H reduction was confirmed via ELISA, which was consistent with our proteomic results. Conclusions: This study provides a comprehensive profile of the CSF proteome in EOAD and identifies three potential EOAD biomarker proteins.

Lipid scrambling is a general feature of protein insertases.

Glycerophospholipids are synthesized primarily in the cytosolic leaflet of the endoplasmic reticulum (ER) membrane and must be equilibrated between bilayer leaflets to allow the ER and membranes derived from it to grow. Lipid equilibration is facilitated by integral membrane proteins called "scramblases." These proteins feature a hydrophilic groove allowing the polar heads of lipids to traverse the hydrophobic membrane interior, similar to a credit card moving through a reader. Nevertheless, despite their fundamental role in membrane expansion and dynamics, the identity of most scramblases has remained elusive. Here, combining biochemical reconstitution and molecular dynamics simulations, we show that lipid scrambling is a general feature of protein insertases, integral membrane proteins which insert polypeptide chains into membranes of the ER and organelles disconnected from vesicle trafficking. Our data indicate that lipid scrambling occurs in the same hydrophilic channel through which protein insertion takes place and that scrambling is abolished in the presence of nascent polypeptide chains. We propose that protein insertases could have a so-far-overlooked role in membrane dynamics as scramblases.

In Situ Hybridization Strategy Constructs Heterogeneous Interfaces to Form Electronically Modulated MoS2/FeS2 as the Anode for High-Performance Lithium-Ion Storage.

The interfacial effect is important for anodes of transition metal dichalcogenides (TMDs) to achieve superior lithium-ion storage performance. In this paper, a MoS2/FeS2 heterojunction is synthesized by a simple hydrothermal reaction to construct the interface effect, and the heterostructure introduces an inherent electric field that accelerates the de-embedding process of lithium ions, improves the electron transfer capability, and effectively mitigates volume expansion. XPS analysis confirms evident chemical interaction between MoS2 and FeS2 via an interfacial covalent bond (Mo-S-Fe). This MoS2/FeS2 anode shows a distinct interfacial effect for efficient interatomic electron migration. The electrochemical performance demonstrated that the discharge capacity can reach up to 1217.8 mA h g-1 at 0.1 A g-1 after 200 cycles, with a capacity retention rate of 72.9%. After 2000 cycles, the capacity retention is about 61.6% at 1.0 A g-1, and the discharge capacity can still reach 638.9 mA h g-1. Electrochemical kinetic analysis indicated an enhanced pseudocapacitance contribution and that the MoS2/FeS2 had sufficient adsorption of lithium ions. This paper therefore argues that this interfacial engineering is an effective solution for designing sulfide-based anodes with good electrochemical properties.

Pre-lithiation strategy to design a high-performance zinc oxide anode for lithium-ion batteries.

Zinc oxide (ZnO) shows great potential as an anode material for advanced energy storage devices owing to its good structural stability and low cost. However, its inferior cycling capacity seriously restricts its practical application. In this work, a pre-lithiation strategy is adopted to construct pre-lithiated ZnO (Li-ZnO) via the facile solid-state reaction method. This well-designed Li-ZnO is polycrystalline, consisting of fine particles. XPS analysis and Raman results confirm the successful pre-lithiation strategy. The pre-lithiation strategy increases the electronic conductivity of Li-ZnO without further carbon coating and suppresses the volume expansion during the electrochemical reaction. As a result, 5 mol% Li-ZnO displays good reversible capacity with a specific capacity of 639 mA h g-1 after 200 cycles at 0.1 A g-1. After 1440 cycles at 1.0 A g-1, the capacity retention is 380 mA h g-1. The pseudocapacitance contribution can reach up to 72.5% at 1.0 mV s-1. Electrochemical kinetic analysis shows that this pre-lithiation strategy can accelerate the lithium-ion diffusion and charge transfer kinetics of the Li-ZnO anode and suppress the pulverization of the electrochemical reaction. This study demonstrates the necessity of developing new anode materials with good cycling stability via this pre-lithiation strategy.

Does Baseline Cognitive Function Predict the Reduction Rate in HDRS-17 Total Scores in First-Episode, Drug-Naïve Patients with Major Depressive Disorder?

Purpose: Major depressive disorder (MDD) is associated with worse cognitive functioning. We aim to examine the association between baseline cognitive functioning and the reduction rate in HDRS-17 total scores and to highlight the predictors of the reduction rate in HDRS-17 total scores in MDD with first-episode, drug-naïve (FED) patients. Patients and Methods: Ninety FED patients were recruited consecutively and evaluated using the 17-item Hamilton Depression Rating Scale (HDRS-17), the 14-item Hamilton Anxiety Scale (HAMA-14), the Functioning Assessment Short Test (FAST) and the MATRICS Consensus Cognitive Battery (MCCB) at baseline and again at week 8. Results: Eighty-four FED patients completed the study. Comparison showed that response group had significantly higher T scores in TMT-A, BACS-SC, WMS-III, BVMT-R, MSCEI and CPT-IP, but showed significantly lower scores in FAST total scores including autonomy, occupational functioning, cognitive functioning, interpersonal relationship than non- response group (all p's< 0.05). Partial correlation analysis also found that the reduction rate in HDRS-17 total scores could be negatively associated with autonomy, cognitive functioning and interpersonal relationship domains as well as total FAST scores, also was further positively associated with T-scores of BACS-SC, CPT-IP and MSCEI in MCCB, even when accounting for potential confounders. Furthermore, the levels of cognitive function domain, autonomy domain in FAST, and BACS-SC, CPT-IP in MCCB may predict the reduction rate in HDRS-17 total scores in FED patients (all p's< 0.05). Conclusion: Our findings underscore significant correlations between baseline functioning and the reduction rate in HDRS-17 total scores in FED patients. Moreover, better baseline cognitive function, autonomy, speed of processing and attention/vigilance are more likely to predict patients' response to antidepressant treatment, indicating pre-treatment better cognitive functioning may be predictors to treatment response in FED.

[Retracted] MicroRNA­203 inhibits the proliferation and invasion of U251 glioblastoma cells by directly targeting PLD2.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the PLD2 western blotting data shown in Fig. 3A and the Transwell invasion assay data shown in Fig. 6 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to Molecular Medicine Reports, or were under consideration for publication at around the same time. In view of the fact that certain of these data had already apparently been published previously, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 9: 503­508, 2014; 10.3892/mmr.2013.1814].

Triosephosphate isomerase 1 may be a risk predictor in laryngeal squamous cell carcinoma: a multi-centered study integrating bulk RNA, single-cell RNA, and protein immunohistochemistry.

BACKGROUND: Although great progress has been made in anti-cancer therapy, the prognosis of laryngeal squamous cell carcinoma (LSCC) patients remains unsatisfied. Quantities of studies demonstrate that glycolytic reprograming is essential for the progression of cancers, where triosephosphate isomerase 1 (TPI1) serves as a catalytic enzyme. However, the clinicopathological significance and potential biological functions of TPI1 underlying LSCC remains obscure. METHODS: We collected in-house 82 LSCC tissue specimens and 56 non-tumor tissue specimens. Tissue microarrays (TMA) and immunohistochemical (IHC) experiments were performed. External LSCC microarrays and bulk RNA sequencing data were integrated to evaluate the expression of TPI1. We used a log-rank test and the CIBERSORT algorithm to assess the prognostic value of TPI1 and its association with the LSCC microenvironment. Malignant laryngeal epithelial cells and immune-stromal cells were identified using inferCNV and CellTypist. We conducted a comprehensive analysis to elucidate the molecular functions of TPI1 in LSCC tissue and single cells using Pearson correlation analysis, high dimensional weighted gene co-expression analysis, gene set enrichment analysis, and clustered regularly interspaced short palindromic repeats (CRISPR) screen. We explored intercellular communication patterns between LSCC single cells and immune-stromal cells and predicted several therapeutic agents targeting TPI1. RESULTS: Based on the in-house TMA and IHC analysis, TPI1 protein was found to have a strong positive expression in the nucleus of LSCC cells but only weakly positive activity in the cytoplasm of normal laryngeal cells (p < 0.0001). Further confirmation of elevated TPI1 mRNA expression was obtained from external datasets, comparing 251 LSCC tissue samples to 136 non-LSCC tissue samples (standardized mean difference = 1.06). The upregulated TPI1 mRNA demonstrated a high discriminative ability between LSCC and non-LSCC tissue (area under the curve = 0.91; sensitivity = 0.87; specificity = 0.79), suggesting its potential as a predictive marker for poor prognosis (p = 0.037). Lower infiltration abundance was found for plasma cells, naïve B cells, monocytes, and neutrophils in TPI-high expression LSCC tissue. Glycolysis and cell cycle were significantly enriched pathways for both LSCC tissue and single cells, where heat shock protein family B member 1, TPI1, and enolase 1 occupied a central position. Four outgoing communication patterns and two incoming communication patterns were identified from the intercellular communication networks. TPI1 was predicted as an oncogene in LSCC, with CRISPR scores less than -1 across 71.43% of the LSCC cell lines. TPI1 was positively correlated with the half maximal inhibitory concentration of gemcitabine and cladribine. CONCLUSIONS: TPI1 is dramatically overexpressed in LSCC than in normal tissue, and the high expression of TPI1 may promote LSCC deterioration through its metabolic and non-metabolic functions. This study contributes to advancing our knowledge of LSCC pathogenesis and may have implications for the development of targeted therapies in the future.