Zero-shot prediction of mutation effects with multimodal deep representation learning guides protein engineering.

Mutations in amino acid sequences can provoke changes in protein function. Accurate and unsupervised prediction of mutation effects is critical in biotechnology and biomedicine, but remains a fundamental challenge. To resolve this challenge, here we present Protein Mutational Effect Predictor (ProMEP), a general and multiple sequence alignment-free method that enables zero-shot prediction of mutation effects. A multimodal deep representation learning model embedded in ProMEP was developed to comprehensively learn both sequence and structure contexts from ~160 million proteins. ProMEP achieves state-of-the-art performance in mutational effect prediction and accomplishes a tremendous improvement in speed, enabling efficient and intelligent protein engineering. Specifically, ProMEP accurately forecasts mutational consequences on the gene-editing enzymes TnpB and TadA, and successfully guides the development of high-performance gene-editing tools with their engineered variants. The gene-editing efficiency of a 5-site mutant of TnpB reaches up to 74.04% (vs 24.66% for the wild type); and the base editing tool developed on the basis of a TadA 15-site mutant (in addition to the A106V/D108N double mutation that renders deoxyadenosine deaminase activity to TadA) exhibits an A-to-G conversion frequency of up to 77.27% (vs 69.80% for ABE8e, a previous TadA-based adenine base editor) with significantly reduced bystander and off-target effects compared to ABE8e. ProMEP not only showcases superior performance in predicting mutational effects on proteins but also demonstrates a great capability to guide protein engineering. Therefore, ProMEP enables efficient exploration of the gigantic protein space and facilitates practical design of proteins, thereby advancing studies in biomedicine and synthetic biology.

Electric Field Generated at the Millisecond Pulse-Polarized Interface Facilitates the Electrolytic Conversion of SO2 into H2S.

Interfacial electric field holds significant importance in determining both the polar molecular configuration and surface coverage during electrocatalysis. This study introduces a methodology leveraging the varying electric dipole moment of SO2 under distinct interfacial electric field strengths to enhance the selectivity of the SO2 electroreduction process. This approach presented the first attempt to utilize pulsed voltage application to the Au/PTFE membrane electrode for the control of the molecular configuration and coverage of SO2 on the electrode surface. Remarkably, the modulation of pulse duration resulted in a substantial inhibition of the hydrogen evolution reaction (HER) (FEH2 < 3%) under millisecond pulse conditions (ta = 10 ms, tc = 300 ms, Ea = -0.8 V (vs Hg/Hg2SO4), Ec = -1.8 V (vs Hg/Hg2SO4)), concomitant with a noteworthy enhancement in H2S selectivity (FEH2S > 97%). A comprehensive analysis, incorporating in situ Raman spectroscopy, electrochemical quartz crystal microbalance, COMSOL simulations, and DFT calculations, corroborated the increased selectivity of H2S products was primarily associated with the inherently large dipole moment of the SO2 molecule. The enhancement of the interfacial electric field induced by millisecond pulses was instrumental in amplifying SO2 coverage, activating SO2, facilitating the formation of the pivotal intermediate product *SOH, and effectively reducing the reaction energy barrier in the SO2 reduction process. These findings provide novel insights into the influences of ion and molecular transport dynamics, as well as the temporal intricacies of competitive pathways during the SO2 electroreduction process. Moreover, it underscores the intrinsic correlation between the electric dipole moment and surface-molecule interaction of the catalyst.

Zno nanoparticles: improving photosynthesis, shoot development, and phyllosphere microbiome composition in tea plants.

BACKGROUND: Nanotechnology holds revolutionary potential in the field of agriculture, with zinc oxide nanoparticles (ZnO NPs) demonstrating advantages in promoting crop growth. Enhanced photosynthetic efficiency is closely linked to improved vigor and superior quality in tea plants, complemented by the beneficial role of phyllosphere microorganisms in maintaining plant health. However, the effects of ZnO NPs on the photosynthesis of tea plants, the sprouting of new shoots, and the community of phyllosphere microorganisms have not been fully investigated. RESULTS: This study investigated the photosynthetic physiological parameters of tea plants under the influence of ZnO NPs, the content of key photosynthetic enzymes such as RubisCO, chlorophyll content, chlorophyll fluorescence parameters, transcriptomic and extensive targeted metabolomic profiles of leaves and new shoots, mineral element composition in these tissues, and the epiphytic and endophytic microbial communities within the phyllosphere. The results indicated that ZnO NPs could enhance the photosynthesis of tea plants, upregulate the expression of some genes related to photosynthesis, increase the accumulation of photosynthetic products, promote the development of new shoots, and alter the content of various mineral elements in the leaves and new shoots of tea plants. Furthermore, the application of ZnO NPs was observed to favorably influence the microbial community structure within the phyllosphere of tea plants. This shift in microbial community dynamics suggests a potential for ZnO NPs to contribute to plant health and productivity by modulating the phyllosphere microbiome. CONCLUSION: This study demonstrates that ZnO NPs have a positive impact on the photosynthesis of tea plants, the sprouting of new shoots, and the community of phyllosphere microorganisms, which can improve the growth condition of tea plants. These findings provide new scientific evidence for the application of ZnO NPs in sustainable agricultural development and contribute to advancing research in nanobiotechnology aimed at enhancing crop yield and quality.

Relationship and mechanisms between internet use and physical exercise among middle- and younger-aged groups.

The "Internet Plus" era has established a closer connection between sports and individuals. This study used data from the 2018 China Family Panel Studies and focused on the middle- and younger-aged population aged 15 to 59 years. Employing a negative binomial regression model, this study empirically analyzed the impact of Internet use on physical exercise and its internal mechanisms among this population. The findings revealed that (1) Internet use significantly promoted physical exercise in the middle- and younger-aged population, with the frequency of physical exercise increasing to 1.549 times the original value; (2) The positive effects of the internet on physical exercise outweighed the negative effects, with online learning and entertainment enhancing physical exercise and online socialization limiting it. Specifically, online learning and entertainment increased the frequency of physical exercise among the middle- and younger-aged population by 0.063 and 0.018, respectively. Online socialization reduced the frequency by 0.023; and (3) The influence of internet use on physical exercise varies; significantly, it positively affects the exercise frequency among individuals over 35 years old and shows a positive correlation with employment status, including both employed individuals and those out of the labor market. The positive role of Internet use in encouraging physical exercise participation among the middle- and young-aged groups should be valued and enhanced.

Dual-stream multi-dependency graph neural network enables precise cancer survival analysis.

Histopathology image-based survival prediction aims to provide a precise assessment of cancer prognosis and can inform personalized treatment decision-making in order to improve patient outcomes. However, existing methods cannot automatically model the complex correlations between numerous morphologically diverse patches in each whole slide image (WSI), thereby preventing them from achieving a more profound understanding and inference of the patient status. To address this, here we propose a novel deep learning framework, termed dual-stream multi-dependency graph neural network (DM-GNN), to enable precise cancer patient survival analysis. Specifically, DM-GNN is structured with the feature updating and global analysis branches to better model each WSI as two graphs based on morphological affinity and global co-activating dependencies. As these two dependencies depict each WSI from distinct but complementary perspectives, the two designed branches of DM-GNN can jointly achieve the multi-view modeling of complex correlations between the patches. Moreover, DM-GNN is also capable of boosting the utilization of dependency information during graph construction by introducing the affinity-guided attention recalibration module as the readout function. This novel module offers increased robustness against feature perturbation, thereby ensuring more reliable and stable predictions. Extensive benchmarking experiments on five TCGA datasets demonstrate that DM-GNN outperforms other state-of-the-art methods and offers interpretable prediction insights based on the morphological depiction of high-attention patches. Overall, DM-GNN represents a powerful and auxiliary tool for personalized cancer prognosis from histopathology images and has great potential to assist clinicians in making personalized treatment decisions and improving patient outcomes.

CYP24A1 affected macrophage polarization through degradation of vitamin D as a candidate biomarker for ovarian cancer prognosis.

Ovarian cancer (OC) is a fatal gynecological malignancy with a poor prognosis in which mitochondria-related genes are involved deeply. In this study, we aim to screen mitochondria-related genes that play a role in OC prognosis and investigate its effects. Through single-cell sequencing technology and bioinformatics analysis, including TCGA ovarian cancer data analysis, gene expression signature analysis (GES), immune infiltration analysis, Gene Ontology (GO) enrichment analysis, Gene Set Enrichment Analysis (GSEA), and Principal Component Analysis (PCA), our findings revealed that CYP24A1 regulated macrophage polarization through vitamin D (VD) degradation and served as a target gene for the second malignant subtype of OC through bioinformatics analyses. For further validation, the expression and function of CYP24A1 in OC cells was investigated. And the expression of CYP24A1 was much higher in carcinoma than in paracancerous tissue, whereas the VD content decreased in the OC cell lines with CYP24A1 overexpression. Moreover, macrophages were polarized towards M1 after the intervention of VD-treated OC cell lines and inhibited the malignant phenotypes of OC. However, the effect could be reversed by overexpressing CYP24A1, resulting in the polarization of M2 macrophages, thereby promoting tumor progression, as verified by constructing xenograft models in vitro. In conclusion, our findings suggested that CYP24A1 induced M2 macrophage polarization through interaction with VD, thus promoting the malignant progression of OC.

Specific immunological characteristics and risk factor of XBB variants re-infection in nasopharyngeal carcinoma patients after BA.5 infection.

OBJECTIVES: The specific humoral immune response resulting from inactivated vaccination following by BA.5 infection, and predictors of XBB variants re-infection in BA.5 infection-recovered nasopharyngeal carcinoma (BA.5-RNPC) patients, were explored. METHODS: Serum SARS-CoV-2 specific antibody levels were assessed using enzyme-linked-immunosorbent-assay. Univariate and multivariate binary logistic regression analyses were conducted to identify factors associated with the magnitude of specific humoral immunity and susceptibility to re-infection by XBB variants. RESULTS: Our data demonstrates that SARS-CoV-2 specific antibody levels were comparable between BA.5-RNPC patients and BA.5 infection-recovered-non-cancerous (BA.5-RNC) individuals. Specifically, serum levels of anti-ancestral-S1-IgG, anti-ancestral-nucleocapsid-protein (NP)-IgG, anti-BA.5-receptor binding domain (RBD)-IgG and anti-XBB.1.1.6-RBD-IgG were higher in BA.5-RNPC patients compared to those without a prior infection. Compared to BA.5-RNPC patients without vaccination, individuals who received inactivated vaccination exhibited significantly higher levels of anti-ancestral-S1-IgG and anti-XBB.1.16-RBD-IgG. Multivariate logistic regression analysis revealed that inactivated vaccination was the most significant predictor of all tested SARS-CoV-2 specific antibodies response. Subsequent analysis indicated that a low globulin level is an independent risk factor for XBB re-infection in BA.5-RNPC patients. CONCLUSIONS: The SARS-CoV-2 specific antibodies have been improved in vaccinated BA.5-RNPC patients. However, the baseline immunity status biomarker IgG is an indicators of XBB variant re-infection risk in BA.5-RNPC patients.

Psychological resilience in the relationship between family function and illness uncertainty among family members of trauma patients in the intensive care unit.

BACKGROUND: Severe trauma accounts for a main factor inducing mortality for individuals aged < 45 years in China, which requires admission to intensive care unit (ICU) to receive comprehensive treatment. Family members of patients with unanticipated and life-threatening trauma during their ICU stays often experience psychosocial distress due to illness uncertainty. Previous research has shown that family function and psychological resilience are associated with illness uncertainty, respectively. However, little is known about the current situation and interacting mechanism between family function, psychological resilience, and illness uncertainty of family members for ICU trauma patients. Therefore, this study focused on exploring the current situation and relationships between these three factors in family members for ICU trauma patients. METHODS: The convenience sampling approach was adopted in the present cross-sectional survey, which involved 230 family members for ICU trauma patients from 34 hospitals in Chongqing, China. Related data were extracted with self-reporting questionnaires, which included sociodemographic characteristic questionnaire, the Family Adaptability, Partnership, Growth, Affection and Resolve Scale (APGAR), the 10-item Connor-Davidson Resilience Scale (10-CD-RISC) and the Mishel's Illness Uncertainty Scale for Family Members (MUIS-FM). Pearson correlation analysis was conducted to examine the correlations between various variables. Additionally, a structural equation model was adopted to assess the mediating effect of psychological resilience on family function and illness uncertainty. RESULTS: According to our results, family members for ICU trauma patients experienced high illness uncertainty with moderate family dysfunction and low psychological resilience. Family function directly affected illness uncertainty and indirectly affected illness uncertainty through psychological resilience in family members of ICU trauma patients. CONCLUSIONS: Family function and psychological resilience are the protective factors for reducing illness uncertainty. Healthcare providers should take effective measures, including family-functioning improvement and resilience-focused interventions, for alleviating illness uncertainty in family members of ICU trauma patients.

Striking Differences in Kendo Headgear.

BACKGROUND:  Kendo, a martial art developed by the samurai, is rooted deep in Japanese culture with traditional armor that has seen little change over the past centuries. Despite its century-old design, kendo helmets are manufactured without third-party testing to verify their quality and effectiveness against head trauma. OBJECTIVE: To evaluate the effectiveness of different helmet stitching patterns and padding materials in mitigating impact forces that could lead to sports-related concussions (SRC) in kendo, and to assess variations in safety performance across different genders and kendo ranks (Dan and Kyu). METHODS: We collected data from 10 kendo practitioners (six males and four females), analyzing over 4,000 strikes using shinai on a sensor-equipped mannequin. Various helmet stitching patterns (ranging from 2 mm to 9 mm) and padding types (polyurethane-based and different thicknesses of cotton-based pads) were tested under controlled conditions simulating realistic impacts encountered in kendo practice. RESULTS: The results indicated that helmets with wider stitching patterns (e.g. 8 mm and 9 mm) generally offered better energy absorption, exhibiting statistically significant lower mean g-forces with a 95% confidence interval compared to tighter patterns (2 mm, 4 mm, 6 mm, and 8 mm x 2 mm) (p < 0.001). Additionally, the polyurethane-based padding outperformed cotton-based padding by a statistically significant reduction of impact force (p < 0.001). Significant differences in striking force were also observed between genders and ranks, with male and higher-rank (Dan) practitioners delivering stronger impacts (both p < 0.001). CONCLUSIONS: This study highlights the critical influence of helmet stitching patterns and padding materials on the protective capabilities against concussions in kendo. Even though helmets with narrower stitching patterns cost more, helmets with wider stitching patterns and polyurethane padding material provide enhanced safety benefits. We do not know how the difference in striking force between genders and ranks affects the outcome of a kendo match.

Two-dimensional Perovskitoids Enhance Stability in Perovskite Solar Cells.

Two-dimensional (2D)/three-dimensional (3D) perovskite heterostructures have played a key role in advancing the performance of perovskite solar cells (PSCs)1,2. However, the migration of cations between 2D and 3D layers results in the disruption of octahedral networks that leads to degradation in performance over time3,4. We hypothesized that perovskitoids, with robust organic-inorganic networks enabled by edge- and face-sharing, could impede ion migration. We explored a set of perovskitoids of varying dimensionality, and found that cation migration within perovskitoid/perovskite heterostructures was suppressed compared to the 2D/3D perovskite case. Increasing the dimensionality of perovskitoids improves charge transport when they are interfaced with 3D perovskite surfaces - this the result of enhanced octahedral connectivity and out-of-plane orientation. The 2D perovskitoid (A6BfP)8Pb7I22 (A6BfP: N-aminohexyl-benz[f]-phthalimide) provides efficient passivation of perovskite surfaces and enables uniform large-area perovskite films. Devices based on perovskitoid/perovskite heterostructures achieve a certified quasi-steady-state power conversion efficiency of 24.6% for centimeter-area PSCs. We removed the fragile hole transport layers and showed stable operation of the underlying perovskitoid/perovskite heterostructure at 85°C for 1,250 hours for encapsulated large-area devices in an air ambient.

α7nAChR-mediated astrocytic activation: a novel mechanism of Xiongzhi Dilong decoction in ameliorating chronic migraine.

ETHNOPHARMACOLOGICAL RELEVANCE: Alpha 7 nicotinic acetylcholine receptor (α7nAChR)-mediated astrocytic activation is closely related to central sensitization of chronic migraine (CM). Xiongzhi Dilong decoction (XZDL), originated from Xiongzhi Shigao decoction of Yi-zong-jin-jian, has been confirmed to relieve CM in experiment and clinic. However, its underlying mechanism for treating CM has not been elucidated. AIM OF THE STUDY: To reveal the underlying mechanisms of XZDL to alleviate CM in vivo focusing mainly on α7nAChR-mediated astrocytic activation and central sensitization in TNC. MATERIALS AND METHODS: CM rat model was established by subcutaneous injection of nitroglycerin (NTG) recurrently, and treated with XZDL simultaneously. Migraine-like behaviors of rats (ear redness, head scratching, and cage climbing) and pain-related reactions (mechanical hind-paw withdrawal threshold) of rats were evaluated before and after NTG injection and XZDL administration at different points in time for nine days. The immunofluorescence single and double staining were applied to detect the levels of CGRP, c-Fos, GFAP and α7nAChR in NTG-induced CM rats. ELISA kits were employed to quantify levels of TNF-α, IL-1ß, and IL-6 in medulla oblongata of CM rats. The expression levels of target proteins were examined using western blotting. Finally, methyllycaconitine citrate (MLA, a specific antagonist of α7nAChR) was applied to further validate the mechanisms of XZDL in vivo. RESULTS: XZDL significantly attenuated the pain-related behaviors of the NTG-induced CM rats, manifesting as constraints of aberrant migraine-like behaviors including elongated latency of ear redness and decreased numbers of head scratching and cage climbing, and increment of mechanical withdrawal threshold. Moreover, XZDL markedly lowered levels of CGRP and c-Fos, as well as inflammatory cytokines (IL-1ß, IL-6 and TNF-α) in CM rats. Furthermore, XZDL significantly enhanced α7nAChR expression and its co-localization with GFAP, while markedly inhibited the expression of GFAP and the activation of JAK2/STAT3/NF-κB pathway in the TNC of CM rats. Finally, blocking α7nAChR with MLA reversed the effects of XZDL on astrocytic activation, central sensitization, and the pain-related behaviors in vivo. CONCLUSION: XZDL inhibited astrocytic activation and central sensitization in NTG-induced CM rats by facilitating α7nAChR expression and suppressing JAK2/STAT3/NF-κB pathway, implying that the regulation of α7nAChR-mediated astrocytic activation represents a novel mechanism of XZDL for relieving CM.

Study of the Effects of Different Ambient Gases and Buoyancy on Hydrogen Jet Characteristics.

Substituting nitrogen with inert gases in an inert gas cycle engine can not only effectively improve engine efficiency but also eliminate NOX emissions in the combustion products. Owing to the low density of hydrogen, jet development is affected by buoyancy. This study explored the effects of different ambient gases, such as Ar, N2, and He, as well as buoyancy, on the hydrogen jet and mixing characteristics based on Schlieren. The results indicated that as the pressure ratio increases, the penetration length and volume of the hydrogen jet increase, whereas the dispersion angle and entrainment ratio decrease. The penetration capacity of the hydrogen jet is strongest in He, followed by N2, and weakest in Ar. Additionally, in He, the hydrogen jet exhibits the smallest dispersion angle, fastest jet volume growth, and largest entrainment ratio. The entrainment ratio of the H2 jet in He is 2.75-3.84 times that of N2 and 4.72-8.3 times that of Ar. In N2 and Ar, the penetration length of the inverted jet after 2.5 ms is approximately 2-4 mm longer than that of the upright jet, indicating that buoyancy has a certain influence on jet development.

Radical resection in a patient with stage IIIA non-small cell lung cancer with the EGFR exon 19 deletion mutation after neoadjuvant targeted therapy with osimertinib: a case report.

Background: With the advent of targeted therapies, the survival rates of patients with locally advanced lung cancer have significantly improved. However, there is limited research on the efficacy of neoadjuvant targeted therapy in resectable advanced non-small cell lung cancer (NSCLC) patients with positive driver genes. This article reports a case of stage IIIA NSCLC with an epidermal growth factor receptor (EGFR) 19del mutation that successfully underwent radical lung cancer surgery following neoadjuvant targeted therapy. By observing the perioperative treatment outcomes and side effects in this patient, we aimed to provide insights and summarize experiences for treating similar cases in the future. Case Description: We report a case of a 54-year-old female diagnosed preoperatively with stage IIIA adenocarcinoma of the left upper lung (cT1cN2M0). The patient's course was complicated by acute sick sinus syndrome and was cured by implanting a permanent pacemaker. After multidisciplinary discussion, it was decided to administer neoadjuvant targeted therapy with osimertinib. Following 6 weeks of treatment, the tumor assessment showed partial response (PR), making the patient eligible for surgery. The patient underwent single-port thoracoscopic left upper lobectomy + mediastinal lymphadenectomy. Intraoperatively, the left hilar lymph nodes were found to be tightly adherent to the apical-anterior branch of the left upper pulmonary artery. The main trunk of the left pulmonary artery was temporarily occluded with a vascular clamp to safely dissect the left upper pulmonary artery. The procedure was completed without conversion to open thoracotomy, achieving an R0 resection. Postoperative pathology confirmed stage IIIA (ypT1bN2M0), and the patient continued adjuvant therapy with osimertinib. Conclusions: Neoadjuvant targeted therapy with osimertinib is expected to become one of the options for neoadjuvant therapy in locally advanced NSCLC with sensitizing EGFR mutations. And for those with advanced lung cancer involving tumors close to the hilum or mediastinal lymph node metastasis, preblocking of the left upper pulmonary artery can help improve surgical safety and better ensure R0 resection.

Unraveling the ultrastructure and dynamics of autophagic vesicles: Insights from advanced imaging techniques.

Autophagy, an intracellular self-degradation process, is governed by a complex interplay of signaling pathways and interactions between proteins and organelles. Its fundamental purpose is to efficiently clear and recycle cellular components that are damaged or redundant. Central to this process are autophagic vesicles, specialized structures that encapsulate targeted cellular elements, playing a pivotal role in autophagy. Despite growing interest in the molecular components of autophagic machinery and their regulatory mechanisms, capturing the detailed ultrastructural dynamics of autophagosome formation continues to present significant challenges. However, recent advancements in microscopy, particularly in electron microscopy, have begun to illuminate the dynamic regulatory processes underpinning autophagy. This review endeavors to provide an exhaustive overview of contemporary research on the ultrastructure of autophagic processes. By synthesizing observations from diverse technological methodologies, this review seeks to deepen our understanding of the genesis of autophagic vesicles, their membrane origins, and the dynamic alterations that transpire during the autophagy process. The aim is to bridge gaps in current knowledge and foster a more comprehensive comprehension of this crucial cellular mechanism.

A Collaborative Approach for Metal Pollution Assessment in Production System of Plastic-Shed Vegetables Near Industrial Areas.

A collaborative assessment approach, including impact index of comprehensive quality (IICQ), food pollution index (FPI), and single factor pollution index (PI), was used to simultaneously select priority metal pollutants and assess metal contamination status in the plastic-shed soil (PSS)-vegetable system of the industrial towns situated in the Yangtze River Delta, China. Overall, significant Cr increment as well as Cd and Cu pollution in PSS existed, which was related to anthropogenic activities, especially industrial wastewater irrigation. The evaluation using PI and FPI demonstrated that priority metal pollutants were Cu and Cd in PSS while Cr and Cd in vegetables. Additionally, the estimation using IICQ method revealed that 23.3% and 13.3% of the sampling sites were sub-moderately and heavily contaminated by metals, respectively. These sites especially with heavy pollution need priority pollution management. These data will be beneficial to metal pollution control in PSS-vegetable system around industrial areas.

Undescribed polyketides from endophytes associated with the critically endangered conifer Abies beshanzuensis.

Four undescribed polyketides, beshanzones A (1) and B (2) as well as beshanhexanols A (3) and B (4), along with three known ones (5-7) were isolated from the rice fermentation of two endophytic fungi associated with the critically endangered Chinese endemic conifer Abies beshanzuensis. γ-Butyrolactone derivatives 1, 2, and 5 were isolated from Phomopsis sp. BSZ-AZ-2, an interesting strain that drawn our attention this time. The cyclohexanol derivatives 3, 4, 6, and 7 were obtained during a follow-up investigation on Penicillium commune BSZ-P-4-1. The chemical structures including absolute configurations of compounds 1-4 were determined by spectroscopic methods, Mo2(OAc)4 induced electronic circular dichroism (IECD), GIAO NMR calculations and DP4+ probability analyses. In particular, compound 2 contains a novel 5/5 bicyclic ring system, which might be biogenetically derived from the known compound 5 through hydrolysis followed by an Aldol reaction. All isolates were evaluated for their antimicrobial activities against a small panel of bacterial and fungal pathogens. Compounds 6 and 7 showed moderate inhibitory activities against Candida albicans, with MIC values of 16 and 32 µg/mL, respectively.

Comparison between MRI-negative and positive results and the predictors for a poor prognosis in patients with idiopathic acute transverse myelitis.

BACKGROUND: Idiopathic acute transverse myelitis (IATM) is a focal inflammatory disorder of the spinal cord that results in motor, sensory, and autonomic dysfunction. However, the comparative analysis of MRI-negative and MRI-positive in IATM patients were rarely reported. OBJECTIVES: The purpose of this study was to compare MRI-negative with MRI-positive groups in IATM patients, analyze the predictors for a poor prognosis, thus explore the relationship between MRI-negative and prognosis. METHODS: We selected 132 patients with first-attack IATM at the First Affiliated Hospital of Nanchang University from May 2018 to May 2022. Patients were divided into MRI-positive and MRI-negative group according to whether there were responsible spinal MRI lesions, and good prognosis and poor prognosis based on whether the EDSS score ≥ 4 at follow-up. The predictive factors of poor prognosis in IATM patients was analyzed by logistic regression models. RESULTS: Of the 132 patients, 107 first-attack patients who fulfilled the criteria for IATM were included in the study. We showed that 43 (40%) patients had a negative spinal cord MRI, while 27 (25%) patients were identified as having a poor prognosis (EDSS score at follow-up ≥ 4). Compared with MRI-negative patients, the MRI-positive group was more likely to have back/neck pain, spinal cord shock and poor prognosis, and the EDSS score at follow-up was higher. We also identified three risk factors for a poor outcome: absence of second-line therapies, high EDSS score at nadir and a positive MRI result. CONCLUSIONS: Compared with MRI-negative group, MRI-positive patients were more likely to have back/neck pain, spinal cord shock and poor prognosis, with a higher EDSS score at follow-up. The absence of second-line therapies, high EDSS score at nadir, and a positive MRI were risk factors for poor outcomes in patients with first-attack IATM. MRI-negative patients may have better prognosis, an active second-line immunotherapy for IATM patients may improve clinical outcome.

18F-FDG PET/CT Radiomics-Based Multimodality Fusion Model for Preoperative Individualized Noninvasive Prediction of Peritoneal Metastasis in Advanced Gastric Cancer.

PURPOSE: This study was designed to develop and validate a machine learning-based, multimodality fusion (MMF) model using 18F-fluorodeoxyglucose (FDG) PET/CT radiomics and kernelled support tensor machine (KSTM), integrated with clinical factors and nuclear medicine experts' diagnoses to individually predict peritoneal metastasis (PM) in advanced gastric cancer (AGC). METHODS: A total of 167 patients receiving preoperative PET/CT and subsequent surgery were included between November 2006 and September 2020 and were divided into a training and testing cohort. The PM status was confirmed via laparoscopic exploration and postoperative pathology. The PET/CT signatures were constructed by classic radiomic, handcrafted-feature-based model and KSTM self-learning-based model. The clinical nomogram was constructed by independent risk factors for PM. Lastly, the PET/CT signatures, clinical nomogram, and experts' diagnoses were fused using evidential reasoning to establish the MMF model. RESULTS: The MMF model showed excellent performance in both cohorts (area under the curve [AUC] 94.16% and 90.84% in training and testing), and demonstrated better prediction accuracy than clinical nomogram or experts' diagnoses (net reclassification improvement p < 0.05). The MMF model also had satisfactory generalization ability, even in mucinous adenocarcinoma and signet ring cell carcinoma which have poor uptake of 18F-FDG (AUC 97.98% and 89.71% in training and testing). CONCLUSIONS: The 18F-FDG PET/CT radiomics-based MMF model may have significant clinical implications in predicting PM in AGC, revealing that it is necessary to combine the information from different modalities for comprehensive prediction of PM.

Lappanolides A-N, fourteen undescribed sesquiterpenoids from Saussurea costus (Syn. Saussurea lappa) and their anti HBV activity.

Lappanolides A-N (1-14), 14 undescribed sesquiterpenoids, along with 23 known ones (15-37), were isolated from the roots of Saussurea costus, which were primarily categorized into eudesmane, guaiane, and germacrane types. Lappanolide A (1) possessed an unprecedented pseudo-disesquiterpenoids. Their structures and absolute configurations were established using physical data analyses (HRESIMS, IR, 1D and 2D NMR) and ECD calculations. All isolated compounds were tested for anti-hepatitis B virus (anti-HBV) activity. Ten compounds (1, 9, 11, 12, 19, 22, 28, 29, 31, and 36) exhibited activities against HBsAg secretions as determined by ELISA assay, with IC50 values ranging from 5.2 to 45.7 µM. In particular, compounds 28 and 29 showed inhibition of HBsAg secretion with IC50 values of 5.28 and 5.30 µM, and CC50 values of 9.85 and 6.37 µM, respectively, though they all exhibited low selectivity. Several compounds displayed cytotoxicity in the MTT assay. Among them, compound 28 was the most notable and was chosen for further study using flow cytometry. The result showed that it significantly induced HepG2 cell arrest in the S phase and induced apoptosis.

Exosomal mRNA in plasma serves as a predictive marker for microvascular invasion in hepatocellular carcinoma.

BACKGROUND AND AIM: There is a pressing need for non-invasive preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). This study investigates the potential of exosome-derived mRNA in plasma as a biomarker for diagnosing MVI. METHODS: Patients with suspected HCC undergoing hepatectomy were prospectively recruited for preoperative peripheral blood collection. Exosomal RNA profiling was conducted using RNA sequencing in the discovery cohort, followed by differential expression analysis to identify candidate targets. We employed multiplexed droplet digital PCR technology to efficiently validate them in a larger sample size cohort. RESULTS: A total of 131 HCC patients were ultimately enrolled, with 37 in the discovery cohort and 94 in the validation cohort. In the validation cohort, the expression levels of RSAD2, PRPSAP1, and HOXA2 were slightly elevated while CHMP4A showed a slight decrease in patients with MVI compared with those without MVI. These trends were consistent with the findings in the discovery cohort, although they did not reach statistical significance (P > 0.05). Notably, the expression level of exosomal PRPSAP1 in plasma was significantly higher in patients with more than 5 MVI than in those without MVI (0.147 vs 0.070, P = 0.035). CONCLUSION: This study unveils the potential of exosome-derived PRPSAP1 in plasma as a promising indicator for predicting MVI status preoperatively.