The association between glymphatic system dysfunction and alterations in cerebral function and structure in patients with white matter hyperintensities.

The objective of this study is to explore the relationship between the glymphatic system and alterations in the structure and function of the brain in white matter hyperintensity (WMH) patients. MRI data were collected from 27 WMH patients and 23 healthy controls. We calculated the along perivascular space (ALPS) indices, the anterior corner distance of the lateral ventricle, and the width of the third ventricle for each subject. The DPABISurf tool was used to calculate the cortical thickness and cortical area. In addition, data processing assistant for resting-state fMRI was used to calculate regional homogeneity, degree centrality, amplitude low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), and voxel-mirrored homotopic connectivity (VMHC). In addition, each WMH patient was evaluated on the Fazekas scale. Finally, the correlation analysis of structural indicators and functional indicators with bilateral ALPS indices was investigated using Spearman correlation analysis. The ALPS indices of WMH patients were lower than those of healthy controls (left: t = -4.949, P < 0.001; right: t = -3.840, P < 0.001). This study found that ALFF, fALFF, regional homogeneity, degree centrality, and VMHC values in some brain regions of WMH patients were alternated (AlphaSim corrected, P < 0.005, cluster size > 26 voxel, rmm value = 5), and the cortical thickness and cortical area of WMH patients showed trend changes (P < 0.01, cluster size > 20 mm2, uncorrected). Interestingly, we found significantly positive correlations between the left ALPS indices and degree centrality values in the superior temporal gyrus (r = 0.494, P = 0.009, P × 5 < 0.05, Bonferroni correction). Our results suggest that glymphatic system impairment is related to the functional centrality of local connections in patients with WMH. This provides a new perspective for understanding the pathological mechanisms of cognitive impairment in the WMH population.

Comparative molecular dynamics simulations provided insights into the mechanisms of cold-adaption of alginate lyases from the PL7 family.

Alginate is an important polysaccharide that is abundant in the marine environments, including the Polar Regions, and bacterial alginate lyases play key roles in its degradation. Many reported alginate lyases show characteristics of cold-adapted enzymes, including relatively low temperature optimum of activities (Topt) and low thermal stabilities. However, the cold-adaption mechanisms of alginate lyases remain unclear. Here, we studied the cold-adaptation mechanisms of alginate lyases by comparing four members of the PL7 family from different environments: AlyC3 from the Arctic ocean (Psychromonas sp. C-3), AlyA1 from the temperate ocean (Zobellia galactanivorans), PA1167 from the human pathogen (Pseudomonas aeruginosa PAO1), and AlyQ from the tropic ocean (Persicobacter sp. CCB-QB2). Sequence comparison and comparative molecular dynamics (MD) simulations revealed two main strategies of cold adaptation. First, the Arctic AlyC3 and temperate AlyA1 increased the flexibility of the loops close to the catalytic center by introducing insertions at these loops. Second, the Arctic AlyC3 increased the electrostatic attractions with the negatively charged substrate by introducing a high portion of positively charged lysine at three of the insertions mentioned above. Furthermore, our study also revealed that the root mean square fluctuation (RMSF) increased greatly when the temperature was increased to Topt or higher, suggesting the RMSF increase temperature as a potential indicator of the cold adaptation level of the PL7 family. This study provided new insights into the cold-adaptation mechanisms of bacterial alginate lyases and the marine carbon cycling at low temperatures.

Isoporous Membrane Mediated Imprinting Mass Spectrometry Imaging for Spatially-Resolved Metabolomics and Rapid Histopathological Diagnosis.

Surface-assisted laser desorption/ionization (SALDI) mass spectrometry imaging (MSI) holds great value in spatial metabolomics and tumor diagnosis. Tissue imprinting on the SALDI target can avoid laser-induced tissue ablation and simplifies the sample preparation. However, the tissue imprinting process always causes lateral diffusion of biomolecules, thereby losing the fidelity of metabolite distribution on tissue. Herein, a membrane-mediated imprinting mass spectrometry imaging (MMI-MSI) strategy is proposed using isoporous nuclepore track-etched membrane as a mediating imprinting layer to selectively transport metabolites through uniform and vertical pores onto silicon nanowires (SiNWs) array. Compared with conventional direct imprinting technique, MMI-MSI can not only exclude the adsorption of large biomolecules but also avoid the lateral diffusion of metabolites. The whole time for MMI-based sample preparation can be reduced to 2 min, and the lipid peak number can increase from 46 to 113 in kidney tissue detection. Meanwhile, higher resolution of MSI can be achieved due to the confinement effect of the pore channel in the diffusion of metabolites. Based on MMI-MSI, the tumor margins of liver cancer can be clearly discriminated and their different subtypes can be precisely classified. This work demonstrates MMI-MSI is a rapid, highly sensitive, robust and high-resolution technique for spatially-resolved metabolomics and pathological diagnosis.

Atomic Pt Sites Anchored in the Interface between Grains on Vacancy-Enriched CeO2 Nanosheets: One-Step Precursor Combustion Synthesis.

Atomic metal catalysts have unique electronic, structural, and catalytic properties, which are widely used in the field of catalysis. However, designing new simple synthesis methods to fabricate atomic metal catalysts is a challenge in catalytic applications. Herein, a one-step precursor combustion strategy is presented that starts directly from precursors of metal salts, using a spontaneous combustion process convert platinum nitrate to atomic Pt sites. The atomic Pt sites with low valence are anchored in the formed interface between grains on vacancy-enriched CeO2 nanosheets. The obtained Pt/CeO2-2 catalyst exhibits much higher three-way catalytic activities at low temperatures than Pt/CeO2-C catalysts prepared using the traditional impregnation method. Density functional theory calculations show that the generated lower valent Pt atoms in the CeO2 interface promote catalytic activity through reducing the energy barrier, and lead to an overall improvement of three-way catalytic activities. This facile strategy provides new insights into the study of the properties and applications of atomic noble metal catalysts.

Two-Step Perovskite Solar Cells with > 25% Efficiency: Unveiling the Hidden Bottom Surface of Perovskite Layer.

While significant efforts in surface engineering have been devoted to the conversion process of lead iodide (PbI2) into perovskite and top surface engineering of perovskite layer with remarkable progress, the exploration of residual PbI2 clusters and the hidden bottom surface on perovskite layer have been limited. In this work, a new strategy involving 1-butyl-3-methylimidazolium acetate (BMIMAc) ionic liquid (IL) additives is developed and it is found that both the cations and the anions in ILs can interact with the perovskite components, thereby regulating the crystallization process and diminishing the residue PbI2 clusters as well as filling vacancies. The introduction of BMIMAc ILs induces the formation of a uniform porous PbI2 film, facilitating better penetration of the second-step organic salt and fostering a more extensive interaction between PbI2 and the organic salt. Surprisingly, the oversized residual PbI2 clusters at the bottom surface of the perovskite layer completely diminish. In addition, advanced depth analysis techniques including depth-resolved grazing-incidence wide-angle X-ray scattering (GIWAXS) and bottom thinning technology are employed for a comprehensive understanding of the reduction in residual PbI2. Leveraging effective PbI2 management and regulation of the perovskite crystallization process, the champion devices achieve a power conversion efficiency (PCE) of 25.06% with long-term stability.

Secondary cavitation bubble dynamics during laser-induced bubble formation in a small container.

We investigated secondary cavitation bubble dynamics during laser-induced bubble formation in a small container with a partially confined free surface and elastic thin walls. We employed high-speed photography to record the dynamics of sub-mm-sized laser-induced bubbles and small secondary bubble clouds. Simultaneous light scattering and acoustic measurements were used to detect the oscillation times of laser-induced bubbles. We observed that the appearance of secondary bubbles coincides with a prolonged collapse phase and with re-oscillations of the laser-induced bubble. We observed an asymmetric distribution of secondary bubbles with a preference for the upstream side of the focus, an absence of secondary bubbles in the immediate vicinity of the laser focus, and a migration of laser-induced bubble toward secondary bubbles at large pulse energies. We found that secondary bubbles are created through heating of impurities to form initial nanobubble nuclei, which are further expanded by rarefaction waves. The rarefaction waves originate from the vibration of the elastic thin walls, which are excited either directly by laser-induced bubble or by bubble-excited liquid-mass oscillations. The oscillation period of thin walls and liquid-mass were Twall = 116 µs and Tlm ≈ 160 µs, respectively. While the amplitude of the wall vibrations increases monotonically with the size of laser-induced bubbles, the amplitude of liquid-mass oscillation undulates with increasing bubble size. This can be attributed to a phase shift between the laser-induced bubble oscillation and the liquid-mass oscillator. Mutual interactions between the laser-induced bubble and secondary bubbles reveal a fast-changing pressure gradient in the liquid. Our study provides a better understanding of laser-induced bubble dynamics in a partially confined environment, which is of practical importance for microfluidics and intraluminal laser surgery.

Bacterial c-di-GMP signaling gene affects mussel larval metamorphosis through outer membrane vesicles and lipopolysaccharides.

Biofilms serve as crucial cues for settlement and metamorphosis in marine invertebrates. Within bacterial systems, c-di-GMP functions as a pivotal signaling molecule regulating both biofilm formation and dispersion. However, the molecular mechanism of how c-di-GMP modulates biofilm-induced larval metamorphosis remains elusive. Our study reveals that the deletion of a c-di-GMP related gene in Pseudoalteromonas marina led to an increase in the level of bacterial c-di-GMP by knockout technique, and the mutant strain had an enhanced ability to produce more outer membrane vesicles (OMVs) and lipopolysaccharides (LPS). The mutant biofilms had higher induction activity for larval metamorphosis in mussels Mytilus coruscus, and OMVs play a major role in the induction activity. We further explored the function of LPS in OMVs. Extracted LPS induced high larval metamorphosis rate, and LPS content were subject to c-di-GMP and LPS-biosynthesis gene. Thus, we postulate that the impact of c-di-GMP on biofilm-induced metamorphosis is mediated through OMVs and LPS.

The complete chloroplast genome sequence of Zanthoxylum ailanthoides Sieb. et. Zucc (Rutaceae): an important medicinal plant.

Zanthoxylum ailanthoides is a deciduous tree, with important medicinal and economic values. The complete chloroplast genome sequence of Z. ailanthoides was assembled and the phylogenetic relationship to other species was inferred in this study. The chloroplast genome is 157,209 bp in length, including two inverted repeats of 26,408 bp, a large single-copy of 86,099 bp and a small single copy of 18,294 bp. Moreover, the chloroplast genome contains 129 genes, including 84 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The overall GC content of the chloroplast genome is 38.4%. The phylogenetic analysis indicated that Z. ailanthoides was grouped with a clade containing the species of Z. multijugum, Z. calcicola, Z. oxyphyllum, Z. stenophyllum, and the genus was closely related to Phellodendron. This study contributes to a better understanding of the phylogenetic relationships among Zanthoxylum species.

Multi-Relational Deep Hashing for Cross-Modal Search.

Deep cross-modal hashing retrieval has recently made significant progress. However, existing methods generally learn hash functions with pairwise or triplet supervisions, which involves learning the relevant information by splicing partial similarity between data pairs; notably, this approach only captures the data similarity locally and incompletely, resulting in sub-optimal retrieval performance. In this paper, we propose a novel Multi-Relational Deep Hashing (MRDH) approach, which can fully bridge the modality gap by comprehensively modeling the similarity relationship between data in different modalities. In more detail, to investigate the inter-modal relationships, we constrain the consistency of cross-modal pairwise similarities to maintain the semantic similarity across modalities. Moreover, to further capture complete similarity information, we design a new similarity metric, which we term cross-modal global similarity, by encouraging hash codes of similar data pairs from different modalities to approach a common center and hash codes for dissimilar pairs to converge to different centers. Adopting this approach enables our model to generate more discriminative hash codes. Extensive experiments on three benchmark datasets demonstrate the superiority of our method on cross-modal hashing retrieval.

Immune checkpoint inhibitor for different age patients with NSCLC in efficacy: A systematic review and meta-analysis.

OBJECTIVE: This article is a Meta-analysis aiming to systematically evaluate the difference in efficacy of immune checkpoint inhibitor in patients with non-small cell lung cancer (NSCLC) by age. METHODS: We performed a Meta-analysis of published randomized controlled trials concerning for patients with NSCLC by age. We compared overall survival among three groups (age <65 years, age 65-75 years, age ≥75 years). Hazard ratios (HRs) and 95% confidence intervals (CIs) were collected and pooled. RESULTS: A total of 10,291 patients from 17 RCTs were included. In the group under age 65 years, immune checkpoint inhibitor can significantly prolong the overall survival of patients with NSCLC (HR = 0.73, 95% CI: 0.66∼0.81, P < 0.00001). In the age 65-75 years group, immune checkpoint inhibitors prolonged overall survival in patients with NSCLC (HR = 0.78, 95% CI:0.71∼0.84, P < 0.00001). However, it has no significant effect on the overall survival of NSCLC patients (HR = 0.88, 95% CI:0.72∼1.08, P > 0.05) in the group older than 75 years. CONCLUSIONS: Immune checkpoint inhibitors prolonged the overall survival of NSCLC patients in the age <65 years group and the age 65-75 years group, but in the age ≥75 years group, there was no significant effect on overall survival. This may be related to innate immune and adaptive immune dysregulation due to "immunosenescence" in older patients.

Heterogeneous Rhodium Single-Atom-Site Catalyst Enables Chemoselective Carbene N-H Bond Insertion.

Transition-metal-catalyzed carbene insertion reactions of a nitrogen-hydrogen bond have emerged as robust and versatile methods for the construction of C-N bonds. While significant progress of homogeneous catalytic metal carbene N-H insertions has been achieved, the control of chemoselectivity in the field remains challenging due to the high electrophilicity of the metal carbene intermediates. Herein, we present an efficient strategy for the synthesis of a rhodium single-atom-site catalyst (Rh-SA) that incorporates a Rh atom surrounded by three nitrogen atoms and one phosphorus atom doped in a carbon support. This Rh-SA catalyst, with a catalyst loading of only 0.15 mol %, exhibited exceptional catalytic performance for heterogeneous carbene insertion with various anilines and heteroaryl amines in combination with diazo esters. Importantly, the heterogeneous catalyst selectively transformed aniline derivatives bearing multiple nucleophilic moieties into single N-H insertion isomers, while the popular homogeneous Rh2(OAc)4 catalyst produced a mixture of overfunctionalized side products. Additionally, similar selectivities for N-H bond insertion with a set of stereoelectronically diverse diazo esters were obtained, highlighting the general applicability of this heterogeneous catalysis approach. On the basis of density functional theory calculations, the observed selectivity of the Rh-SA catalyst was attributed to the insertion barriers and the accelerated proton transfer assisted by the phosphorus atom in the support. Overall, this investigation of heterogeneous metal-catalyzed carbene insertion underscores the potential of single-atom-site catalysis as a powerful and complementary tool in organic synthesis.

Prospect of value and application of transcutaneous electrical acupoint stimulation to control blood pressure in proactive healthcare perspective. / 主动健康视域下经皮穴位电刺激调控血压的价值与应用展望.

Hypertension is a global problem threatening human health and life. Although there are many antihypertensive drugs, the low compliance of medication affects its efficacy, and the effect in regulating hypertension has become increasingly prominent. Focusing on the new trend of proactive healthcare management, in the present paper, we made a summary about the status and existing problems of transcutaneous electrical acupoint stimulation (TEAS) in the regulation of blood pressure, and put forward some suggestions, such as selecting acupoints based on classical acupuncture theory to highlight the advantages of TEAS to control blood pressure as a whole, optimizing and screening the parameters of TEAS in the regulation of blood pressure, expanding the research observation indexes etc. We also made a prospect about its future application, hoping to provide new ideas for the proactive regulation, whole-process regulation and integrated regulation of blood pressure.

Weakly Confined Organic-Inorganic Halide Perovskite Quantum Dots as High-Purity Room-Temperature Single Photon Sources.

Colloidal perovskite quantum dots (PQDs) have emerged as highly promising single photon emitters for quantum information applications. Presently, most strategies have focused on leveraging quantum confinement to increase the nonradiative Auger recombination (AR) rate to enhance single-photon (SP) purity in all-inorganic CsPbBr3 QDs. However, this also increases the fluorescence intermittency. Achieving high SP purity and blinking mitigation simultaneously remains a significant challenge. Here, we transcend this limitation with room-temperature synthesized weakly confined hybrid organic-inorganic perovskite (HOIP) QDs. Superior single photon purity with a low g(2)(0) < 0.07 ± 0.03 and a nearly blinking-free behavior (ON-state fraction >95%) in 11 nm FAPbBr3 QDs are achieved at room temperature, attributed to their long exciton lifetimes (τX) and short biexciton lifetimes (τXX). The significance of the organic A-cation is further validated using the mixed-cation FAxCs1-xPbBr3. Theoretical calculations utilizing a combination of the Bethe-Salpeter (BSE) and k·p approaches point toward the modulation of the dielectric constants by the organic cations. Importantly, our findings provide valuable insights into an additional lever for engineering facile-synthesized room-temperature PQD single photon sources.

TOB1 modulates neutrophil phenotypes to influence gastric cancer progression and immunotherapy efficacy.

Introduction: The ErbB-2.1(TOB1) signaling transducer protein is a tumor-suppressive protein that actively suppresses the malignant phenotype of gastric cancer cells. Yet, TOB1 negatively regulates the activation and growth of different immune cells. Understanding the expression and role of TOB1 in the gastric cancer immune environment is crucial to maximize its potential in targeted immunotherapy. Methods: This study employed multiplex immunofluorescence analysis to precisely delineate and quantify the expression of TOB1 in immune cells within gastric cancer tissue microarrays. Univariate and multivariate Cox analyses were performed to assess the influence of clinical-pathological parameters, immune cells, TOB1, and double-positive cells on the prognosis of gastric cancer patients. Subsequent experiments included co-culture assays of si-TOB1-transfected neutrophils with AGS or HGC-27 cells, along with EdU, invasion, migration assays, and bioinformatics analyses, aimed at elucidating the mechanisms through which TOB1 in neutrophils impacts the prognosis of gastric cancer patients. Results: We remarkably revealed that TOB1 exhibits varying expression levels in both the nucleus (nTOB1) and cytoplasm (cTOB1) of diverse immune cell populations, including CD8+ T cells, CD66b+ neutrophils, FOXP3+ Tregs, CD20+ B cells, CD4+ T cells, and CD68+ macrophages within gastric cancer and paracancerous tissues. Significantly, TOB1 was notably concentrated in CD66b+ neutrophils. Survival analysis showed that a higher density of cTOB1/nTOB1+CD66b+ neutrophils was linked to a better prognosis. Subsequent experiments revealed that, following stimulation with the supernatant of tumor tissue culture, the levels of TOB1 protein and mRNA in neutrophils decreased, accompanied by enhanced apoptosis. HL-60 cells were successfully induced to neutrophil-like cells by DMSO. Neutrophils-like cells with attenuated TOB1 gene expression by si-TOB1 demonstrated heightened apoptosis, consequently fostering a malignant phenotype in AGS and HCG-27 cells upon co-cultivation. The subsequent analysis of the datasets from TCGA and TIMER2 revealed that patients with high levels of TOB1 combined neutrophils showed better immunotherapy response. Discussion: This study significantly advances our comprehension of TOB1's role within the immune microenvironment of gastric cancer, offering promising therapeutic targets for immunotherapy in this context.

Association between reversal agents (sugammadex vs. neostigmine) for neuromuscular block and postoperative pulmonary complications: A retrospective analysis.

AIMS: Residual neuromuscular blockade has been linked to pulmonary complications in the postoperative period. This study aimed to determine whether sugammadex was associated with a lower risk of postoperative pulmonary complications (PPCs) compared with neostigmine. METHODS: This retrospective cohort study was conducted in a tertiary academic medical center. Patients ≥18 year of age undergoing noncardiac surgical procedures with general anesthesia and mechanical ventilation were enrolled between January 2019 and September 2021. We identified all patients receiving rocuronium and reversal with neostigmine or sugammadex via electronic medical record review. The primary endpoint was a composite of PPCs (including pneumonia, atelectasis, respiratory failure, pulmonary embolism, pleural effusion, or pneumothorax). The incidence of PPCs was compared using propensity score analysis. RESULTS: A total of 1786 patients were included in this study. Among these patients, 976 (54.6%) received neostigmine, and 810 (45.4%) received sugammadex. In the whole sample, PPCs occurred in 81 (4.54%) subjects (7.04% sugammadex vs. 2.46% neostigmine). Baseline covariates were well balanced between groups after overlap weighting. Patients in the sugammadex group had similar risk (overlap weighting OR: 0.75; 95% CI: 0.40 to 1.41) compared to neostigmine. The sensitivity analysis showed consistent results. In subgroup analysis, the interaction P-value for the reversal agents stratified by surgery duration was 0.011. CONCLUSION: There was no significant difference in the rate of PPCs when the neuromuscular blockade was reversed with sugammadex compared to neostigmine. Patients undergoing prolonged surgery may benefit from sugammadex, which needs to be further investigated.

Roegneria yenchiana: A new species in the Triticeae (Poaceae) from the Hengduan Mountain region.

Roegneria yenchiana sp. nov. (Triticeae) is a new species collected from Shangri-la of Yunnan Province in China based on morphological, cytological, and molecular data. It is morphologically characterized by one spikelet per node, rectangular glums, awns flanked by two short mucros in lemmas, distinguished from other species of Roegneria. The genomic in situ hybridization results indicate that R. yenchiana is an allotetraploid, and its genomic constitution is StY. Phylogenetic analyses based on multiple loci suggested that R. yenchiana is closely related to Pseudoroegneria and Roegneria, and the Pseudoroegneria served as the maternal donors during its polyploid speciation.

New Antibacterial Peptaibiotics against Plant and Fish Pathogens from the Deep-Sea-Derived Fungus Simplicillium obclavatum EIODSF 020.

Bacterial diseases could severely harm agricultural production. To develop new antibacterial agents, the secondary metabolites of a deep-sea-derived fungus Simplicillium obclavatum EIODSF 020 with antibacterial activities against plant and fish pathogens were investigated by a bioassay-guided approach, which led to the isolation of 11 new peptaibiotics, simplicpeptaibs A-K (1-11). They contain 16-19 residues, including ß-alanine, tyrosine, or tyrosine O-sulfate, that were rarely present in peptaibiotics. Their structures were elucidated by spectroscopic analyses (NMR, HRMS, HRMS2, and ECD) and Marfey's method. The primary and secondary structures of novel sulfated peptaibiotic 9 were reconfirmed by single-crystal X-ray diffraction analysis. Genome sequencing of S. obclavatum EIODSF 020 allowed the detection of a gene cluster encoding two individual NRPSs (totally containing 19 modules) that was closely related to simplicpeptaib biosynthesis. Antibacterial investigations of 1-11 together with the previously isolated linear and cyclic peptides from this strain suggested the antibacterial property of this fungus was attributed to the peptaibiotics and cyclic lipopeptides. Among them, compounds 4, 6, 7, and 9 showed significant activity against the tobacco pathogen Ralstonia solanacearum or tilapia pathogens Streptococcus iniae and Streptococcus agalactiae. The antibacterial activity of 6 against R. solanacearum could be enhanced by the addition of 1% NaCl. The structure-bioactivity relationship of simplicpeptaibs was discussed.

Research Progress on the Experimental Model and Underlying Mechanistic Studies of Tension-Type Headaches.

PURPOSE OF REVIEW: Tension-type headaches (TTH) significantly diminish patients' quality of life and increase absenteeism, thereby imposing a substantial economic burden. Animal models are essential tools for studying disease mechanisms and drug development. However, until now, little focus has been placed on summarizing the animal models of TTH and associated mechanistic studies. This narrative review discusses the current animal models of TTH and related mechanistic studies to provide insights into the pathophysiological mechanisms of and treatments for TTH. RECENT FINDINGS: The primary method for constructing an animal model of TTH involves injecting a solution of pain relievers, such as adenosine triphosphate, nerve growth factor, or a high concentration of salt solution, into the neck to initiate harmful cervical muscle responses. This model enables the examination of the interaction between peripheral muscles and central sensitization, which is crucial for understanding the pathophysiology of TTH. Mechanistic studies based on this model have investigated the effect of the P2X receptor antagonist, P2X7 receptor blockade, the P2Y1 receptor agonist 2-MESADP, P2Y1 receptor antagonist MRS2179, nitric oxide synthase inhibitors, and acetylsalicylic acid. Despite notable advancements, the current model of TTH has limitations, including surgical complexity and the inability to replicate chronic tension-type headache (CTTH). To gain a more comprehensive understanding and develop more effective treatment methods, future studies should focus on simplifying surgical procedures, examining other predisposing factors, and establishing a model for chronic TTH. This will offer a deeper insight into the pathophysiological mechanism of TTH and pave the way for improved treatment approaches.

MA-PEP: A novel anticancer peptide prediction framework with multimodal feature fusion based on attention mechanism.

AntiCancer Peptides (ACPs) have emerged as promising therapeutic agents for cancer treatment. The time-consuming and costly nature of wet-lab discriminatory methods has spurred the development of various machine learning and deep learning-based ACP classification methods. Nonetheless, current methods encountered challenges in efficiently integrating features from various peptide modalities, thereby limiting a more comprehensive understanding of ACPs and further restricting the improvement of prediction model performance. In this study, we introduce a novel ACP prediction method, MA-PEP, which leverages multiple attention mechanisms for feature enhancement and fusion to improve ACP prediction. By integrating the enhanced molecular-level chemical features and sequence information of peptides, MA-PEP demonstrates superior prediction performance across several benchmark datasets, highlighting its efficacy in ACP prediction. Moreover, the visual analysis and case studies further demonstrate MA-PEP's reliable feature extraction capability and its promise in the realm of ACP exploration. The code and datasets for MA-PEP are available at https://github.com/liangxiaodata/MA-PEP.

Primary pulmonary histiocytic sarcoma with high PD-L1 expression benefited from immunotherapy: A case report and bioinformatic analysis.

Histiocytic sarcoma is an aggressive haematopoietic malignancy accounting for less than 1% of haematolymphoid neoplasms with a diagnosis based on morphology and immunophenotype of tissue biopsies with a very poor prognosis. Here, we report a 45-year-old man who was diagnosed with primary pulmonary histiocytic sarcoma with systemic metastases, with partial remission (PR) treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy, but it relapsed soon after therapy above. Tests demonstrated that TMB was 21 Muts/Mb PD-L1 expression was 90% positive, and the disease has been well-controlled over 3 years using immune checkpoint inhibitors (nivolumab and pembrolizumab). Bioinformatic pan-cancer analysis verified that there was the highest genetic alteration frequency of PD-L1 in which amplification accounted for the majority of sarcoma tumour samples. Following that, we found that the genetic alteration of PD-L1 was associated with poor prognosis in sarcoma patients in terms of overall survival (OS) (p = 1.51 × 10-4 ), progress-free survival (PFS) (p = 4.90 × 10-2 ) and disease-specific survival (DSS) (p = 4.90 × 10-2 ). To our knowledge, this may be the first reported case with high PD-L1 expression in primary pulmonary histiocytic sarcoma who may benefit from immunotherapy such as nivolumab and pembrolizumab significantly and safely.