Background: This study aimed to investigate the safety and efficacy of preoperative targeted immunotherapy followed by surgical resection for hepatocellular carcinoma (HCC) patients with macrovascular invasion. Method: Clinical information of HCC patients with macrovascular invasion was collected from four medical centers. These patients were divided into two cohorts: the upfront surgery group (n=40) and the neoadjuvant group (n=22). Comparisons between the two groups were made with appropriate statistical methods. Results: HCC Patients with macrovascular invasion in the neoadjuvant group were associated with increased incidence of postoperative ascites (72.73% vs. 37.5%, P=0.008), but shorter postoperative hospital stay (10 days vs. 14 days, P=0.032). Furthermore, targeted immunotherapy followed by surgical resection significantly reduced the postoperative recurrence rate at both 3 months and 1 year (9% versus 28.9%, 32.1% versus 67.9%, respectively; P=0.018), but increased the postoperative nononcologic mortality rate within 1 year (20.1% vs. 2.8%; P= 0.036). Conclusion: For HCC patients with macrovascular invasion, preoperative targeted immunotherapy significantly decreased the postoperative tumor recurrence rate while maintaining relative safety, but such a treatment may also result in chronic liver damage and increased risk of nononcologic mortality.
Phylogenetic and morphological analyses on Perenniporia s.l. were carried out. Phylogenies on Perenniporia s.l. are reconstructed with two loci DNA sequences including the internal transcribed spacer (ITS) regions and the large subunit (nLSU). Two new species from Yunnan Province, southwest China, Perenniporiaprunicola and P.rosicola in Perenniporia s.l., are illustrated and described. Perenniporiaprunicola is characterised by the perennial and resupinate basidiomata with a clay pink pore surface when fresh, a trimitic hyphal system, the presence of clavate to fusiform hymenial cystidia, ellipsoid to broadly ellipsoid basidiospores measuring 4.8-6.2 × 3.6-4.5 µm. Perenniporiarosicola is characterised by annual and resupinate basidiomata with a white pore surface when fresh, a dimitic hyphal system, the presence of dendrohyphidia, broadly ellipsoid to subglobose basidiospores measuring 5-5.8 × 4-5.2 µm. In addition, Crassisporus is a genus in Perenniporia s.l., in which two new combinations Crassisporusminutus and C.mollissimus are proposed. Main morphological characteristics of species related to new taxa are also provided.
A series of novel near-infrared (NIR) xanthene-chalcone fluorophores were constructed through a modular synthesis with the electron-donating xanthene moiety and the electron-withdrawing chalcone moiety. These fluorophores are convenient for fluorescence imaging in living cells, benefiting from their NIR emissions (650-710 nm), large Stokes shifts (>100 nm), moderate quantum yields and low cytotoxicity. The substituted hydroxyl group of the xanthene-chalcone fluorophore HCA-E facilitates the development of multifunctional fluorescent probes. As an example, a highly sensitive and selective probe N-HCA-E for glutathione (GSH) detection was developed based on the fluorophore HCA-E. A 4-nitrobenzenesulfonyl (4-Ns) group was introduced to cage the hydroxyl group of HCA-E, which was used as a selective recognition site for the thiol of GSH and an effective fluorescence quencher. Probe N-HCA-E revealed NIR "turn-on" fluorescence (709 nm) for endogenous and exogenous GSH detection in lysosomes with a large Stokes shift (129 nm) and high anti-interference ability.
This study aimed to assess the diagnostic value of [18F]AlF-thretide PET/CT in patients with newly diagnosed prostate cancer (PCa). Methods: In total, 49 patients with biopsy-proven PCa were enrolled in this prospective study. All patients underwent [18F]AlF-thretide PET/CT, and the scoring system of the PRIMARY trial was used for PET image analysis. The dosimetry evaluation of [18F]AlF-thretide was performed on 3 patients. Pathologic examination was used as the reference standard to evaluate the location, number, size, and Gleason score of tumors, for comparison with the [18F]AlF-thretide PET/CT results. PSMA expression was evaluated by immunohistochemical staining. Results: All patients tolerated the [18F]AlF-thretide PET/CT well. The total effective dose of [18F]AlF-thretide was 1.16E-02 mSv/MBq. For patient-based analysis of intraprostatic tumors, 46 of 49 (93.9%) patients showed pathologic uptake on [18F]AlF-thretide PET/CT. For lesion-based analysis of intraprostatic tumors, the sensitivity and positive predictive value for [18F]AlF-thretide PET/CT were 58.2% and 90.5%, respectively. Delayed images can detect more lesions than standard images (n = 57 vs. 49, P = 0.005), and the SUVmax and tumor-to-background ratio of the former were higher than those of the latter (SUVmax: 14.5 ± 16.7 vs. 11.4 ± 13.6, P < 0.001; tumor-to-background ratio: 37.1 ± 42.3 vs. 23.1 ± 27.4, P < 0.001). The receiver-operating-characteristic curve analysis showed that the areas under the curve for PRIMARY score-predicted true-positive and false-positive lesions were significantly higher than those for the SUVmax of standard images (P = 0.015) and seemed higher than those for the SUVmax of delayed images (P = 0.257). [18F]AlF-thretide PET/CT showed a higher detection rate than multiparametric MRI for all intraprostatic foci (53.5% vs. 40.8%, P = 0.012) and clinically significant PCa (75.0% vs. 61.4%, P = 0.031). Conclusion: [18F]AlF-thretide PET/CT showed high diagnostic value for patients with primary PCa and can be used as an excellent imaging modality for preoperative evaluation of PCa patients.
BACKGROUND: Hemodynamic factors play an important role in aneurysm initiation, growth, rupture, and recurrence, while the mechanism of the hemodynamic characteristics is still controversial. A unique model of multiple aneurysms (initiation, growth, rupture, and recurrence) is helpful to avoids the confounders and further explore the possible hemodynamic mechanisms of aneurysm in different states. METHODS: We present a model with multiple aneurysms, and including the states of initiation, growth, rupture, and recurrence, discuss the proposed mechanisms, and describe computational fluid dynamic model that was used to evaluate the likely hemodynamic effect of different states of the aneurysms. RESULTS: The hemodynamic analysis suggests that high flow impingement and high WSS distribution at normal parent artery was found before aneurysmal initiation. The WSS distribution and flow velocity were decreased in the new sac after aneurysmal growth. Low WSS was the risk hemodynamic factor for aneurysmal rupture. High flow concentration region on the neck plane after coil embolization still marked in recanalized aneurysm. CONCLUSIONS: Associations have been identified between high flow impingement and aneurysm recanalization, while low WSS is linked to the rupture of aneurysms. High flow concentration and high WSS distribution at normal artery associated with aneurysm initiation and growth, while after growth, the high-risk hemodynamics of aneurysm rupture was occurred, which is low WSS at aneurysm dome.
Background: The association between pH values and outcome for patients after out-of-hospital cardiac arrest (OHCA) was not fully elucidated; besides, the relationship of change in pH values and neurological outcome was unknown. The aim was to explore the association of pH values as well as change in pH values and neurological outcome for OHCA cardiac patients. Methods: The adult patients with non-traumatic out-of-hospital cardiac arrest, shock-refractory ventricular fibrillation or pulseless ventricular tachycardia, and at least two arterial blood gases analysis recorded after admission were included. The change in pH values is calculated as the difference between the second and first pH value, and divided by time interval got the rate of change in pH values. The primary outcome was modified Rankin Score (mRS), dichotomized to good (mRS 0-3) and poor (mRS 4-6) outcomes at hospital discharge. The independent relationship of the first pH value, second pH value, and changes in pH values with neurological outcome was investigated with multivariable logistic regression models, respectively. Results: A total of 1388 adult patients were included for analysis, of which 514 (37%) had good neurological outcome. The median first pH value and second pH value after admission were 7.21 (interquartile range [IQR] 7.09-7.29) and 7.28 (IQR 7.20-7.36), respectively. The median absolute, relative change, and rate of changes in pH values were 0.08 (IQR 0.01-0.16), 1.10% (IQR 0.11-2.22%), and 0.02 (IQR 0-0.06) per hour, respectively. After adjusting for confounders, the higher first pH value (odds ratio [OR] 3.81, confidence interval [CI] 1.60-9.24, P = 0.003) and higher second pH value (OR 9.54, CI 3.45-26.87, P < 0.001) after admission were associated with good neurological outcome, respectively. The absolute (OR 1.58, CI 0.58-4.30, P = 0.368) and relative (OR 1.03, CI 0.96-1.11, P = 0.399) change as well as the rate of change (OR 0.98, CI 0.33-2.71, P = 974) in pH values were not associated with neurological outcome. Conclusions: For OHCA patients, abnormality in pH values was very common, with a more acidic pH value indicating poor neurological outcome. However, the change in pH values was not associated with outcomes.
Periodontitis, a chronic infectious disease leading to gingival atrophy and potential tooth loss through alveolar bone resorption, is closely linked to the oral microbiome. Fusobacterium nucleatum, known to facilitate late-stage bacterial colonization in the oral microbiome, plays a crucial role in the onset of periodontitis. Controlling F. nucleatum abundance is vital for preventing and treating periodontal disease. Photodynamic therapy combined with 5-aminolevulinic acid (ALA-PDT) has been reported to be bactericidal against Pseudomonas aeruginosa and Staphylococcus aureus. We aimed to investigate the bactericidal potential of ALA-PDT against F. nucleatum, which was evaluated by examining the impact of varying 5-ALA concentrations, culture time, and light intensity. After ALA-PDT treatment, DNA was extracted from interdental plaque samples collected from 10 volunteers and sequenced using the Illumina MiSeq platform. To further elucidate the bactericidal mechanism of ALA-PDT, porphyrins were extracted from F. nucleatum following cultivation with 5-ALA and subsequently analyzed using fluorescence spectra. ALA-PDT showed a significant bactericidal effect against F. nucleatum. Its bactericidal activity demonstrated a positive correlation with culture time and light intensity. Microbiota analysis revealed no significant alteration in α-diversity within the ALA-PDT group, although there was a noteworthy reduction in the proportion of the genus Fusobacterium. Furthermore, fluorescence spectral analysis indicated that F. nucleatum produced an excitable photosensitive substance following the addition of 5-ALA. Overall, if further studies confirm these results, this combined therapy could be an effective strategy for reducing the prevalence of periodontitis.
We have established a facile and efficient protocol for the generation of germyl radicals by employing photo-excited electron transfer (ET) in an electron donor-acceptor (EDA) complex to drive hydrogen-atom transfer (HAT) from germyl hydride (R3GeH). Using a catalytic amount of EDA complex of commercially available thiol and benzophenone derivatives, the ET-HAT cycle smoothly proceeds simply upon blue-light irradiation without any transition metal or photocatalyst. This protocol also affords silyl radical from silyl hydride.
The brachial plexus injury (BPI) is one of the most severe types of peripheral nerve injuries, often caused by upper limb traction injury. In clinic, the surgery is widely used to treat the BPI. However, surgery may need to be performed multiple times at different stages, which carries risks and brings heavy economic burden. In non-surgical treatment, splinting, local injection of corticosteroids, and oral corticosteroids can achieve significant short-term benefits, but they are prone to recurrence and may cause complications of mechanical or chemical nerve damage. In this report, we present a case of a 46-year-old female patient with BPI. The patient had difficulty in raising, flexing and extending of the left upper limb, and accompanied with the soreness and pain of neck and shoulder. After 3 months of EA treatment, a significant reduction in the inner diameter of the left C5 to C7 root at the outlet of brachial plexus nerve was detected by musculoskeletal ultrasound, and the soreness and pain in the left neck and shoulder were significantly reduced. The soreness and pain in the left neck and shoulder did not recur for 2 years. Case summary: The patient is a 46-year-old female with BPI. She experienced difficult in lifting, flexing and extending of the left upper limb, which accompanied by soreness and pain in the left neck and shoulder. After 3 months of EA treatment, the patient's pain and limb's movement disorder was improved. After 2 years of follow-up, the patient's left neck and shoulder showed no further pain. Conclusion: EA has shown satisfied efficacy in BPI, improving limb restrictions and relieving pain in patients for at least 2 years.
SCAP plays a central role in controlling lipid homeostasis by activating SREBP-1, a master transcription factor in controlling fatty acid (FA) synthesis. However, how SCAP expression is regulated in human cancer cells remains unknown. Here, we revealed that STAT3 binds to the promoter of SCAP to activate its expression across multiple cancer cell types. Moreover, we identified that STAT3 also concurrently interacts with the promoter of SREBF1 gene (encoding SREBP-1), amplifying its expression. This dual action by STAT3 collaboratively heightens FA synthesis. Pharmacological inhibition of STAT3 significantly reduces the levels of unsaturated FAs and phospholipids bearing unsaturated FA chains by reducing the SCAP-SREBP-1 signaling axis and its downstream effector SCD1. Examination of clinical samples from patients with glioblastoma, the most lethal brain tumor, demonstrates a substantial co-expression of STAT3, SCAP, SREBP-1, and SCD1. These findings unveil STAT3 directly regulates the expression of SCAP and SREBP-1 to promote FA synthesis, ultimately fueling tumor progression.
Introduction: This study investigates the mechanisms linking students' perceived teacher support with math anxiety, focusing on the mediating roles of the teacher-student relationship and mathematics self-efficacy. Methods: The research was conducted with 401 fifth-grade students in China, utilizing scales for Students' Perceived Teacher Support, Teacher-Student Relationship, Math Self-Efficacy, and Math Anxiety. Results: Findings revealed that student-perceived math teacher support, teacher-student relationship, and math self-efficacy were all significantly negatively correlated with math anxiety. It was notably found that student-perceived math teacher support influenced math anxiety through the chain mediation of teacher-student relationship and math self-efficacy. Additionally, the effect of students' perceived emotional support from math teachers on math anxiety, mediated by teacher-student relationship intimacy, was significant only among male students. Discussion: These results underscore the importance of fostering positive teacher-student interactions and enhancing self-efficacy to reduce math anxiety among primary school students. The gender-specific findings regarding emotional support and relationship intimacy highlight the need for tailored strategies in addressing math anxiety.
Background: Accurate preoperative prediction of glioma is crucial for developing individualized treatment decisions and assessing prognosis. In this study, we aimed to establish and evaluate the value of integrated models by incorporating the intratumoral and peritumoral features from conventional MRI and clinical characteristics in the prediction of glioma grade. Methods: A total of 213 glioma patients from two centers were included in the retrospective analysis, among which, 132 patients were classified as the training cohort and internal validation set, and the remaining 81 patients were zoned as the independent external testing cohort. A total of 7728 features were extracted from MRI sequences and various volumes of interest (VOIs). After feature selection, 30 radiomic models depended on five sets of machine learning classifiers, different MRI sequences, and four different combinations of predictive feature sources, including features from the intratumoral region only, features from the peritumoral edema region only, features from the fusion area including intratumoral and peritumoral edema region (VOI-fusion), and features from the intratumoral region with the addition of features from peritumoral edema region (feature-fusion), were established to select the optimal model. A nomogram based on the clinical parameter and optimal radiomic model was constructed for predicting glioma grade in clinical practice. Results: The intratumoral radiomic models based on contrast-enhanced T1-weighted and T2-flair sequences outperformed those based on a single MRI sequence. Moreover, the internal validation and independent external test underscored that the XGBoost machine learning classifier, incorporating features extracted from VOI-fusion, showed superior predictive efficiency in differentiating between low-grade gliomas (LGG) and high-grade gliomas (HGG), with an AUC of 0.805 in the external test. The radiomic models of VOI-fusion yielded higher prediction efficiency than those of feature-fusion. Additionally, the developed nomogram presented an optimal predictive efficacy with an AUC of 0.825 in the testing cohort. Conclusion: This study systematically investigated the effect of intratumoral and peritumoral radiomics to predict glioma grading with conventional MRI. The optimal model was the XGBoost classifier coupled radiomic model based on VOI-fusion. The radiomic models that depended on VOI-fusion outperformed those that depended on feature-fusion, suggesting that peritumoral features should be rationally utilized in radiomic studies.
Imines are essential intermediates in organic transformations, and is generally produced by dehydrogenative condensation of alcohols and amines with the assist of specialized catalysts and additives. Heterogeneous photocatalysis provides a sustainable platform for such process without the using of toxic oxidants, yet a functionalized photocatalyst with optimized co-adsorption of reactants needs to be developed to promote the stoichiometric oxidative condensation under ambient conditions. Here, we show that benzyl alcohol and aniline adsorb non-interferingly on the Fe node and the linker sites of the MIL-53(Fe) metal organic frameworks (MOFs), respectively. The co-adsorption of both reactants barely influences the reduction of molecular oxygen to generate oxygen radicals, resulting in efficient formation of benzaldehyde under visible light. Additionally, the weak adsorption of water together with surface acidity of the MIL-53(Fe) promote a rapid condensation of benzaldehyde with aniline and the depletion of generated water, achieving an efficient C-N bond creation for a wide range of substrates.
Construction of air filter membranes bearing prominent collecting and transferring capability is highly desirable for detecting airborne pathogens but remains challenging. Here, a hyaluronic acid air filter membrane (HAFM) with tunable heterogeneous micro-nano porous structures is straightforwardly constructed through the ethanol-induced phase separation strategy. Airborne pathogens can be trapped and collected by HAFM with high performance due to the ideal trade-off between removal efficiency and pressure drop. By exempting the sample elution and extraction processes, the HAFM after filtration sampling can not only directly disperse on the agar plate for colony culture but also turn to an aqueous solution for centrifugal enrichment, which significantly reduces the damage and losses of the captured microorganisms. The following combination with ATP bioluminescence endows the HAFM with a real-time quantitative detection function for the captured airborne pathogens. Benefiting from high-efficiency sampling and non-traumatic transfer of airborne pathogens, the real-world bioaerosol concentration can be facilely evaluated by the HAFM-based ATP assay. This work thus not only provides a feasible strategy to fabricate air filter membranes for efficient microbial collection and enrichment but also sheds light on designing advanced protocols for real-time detection of bioaerosols in the field.
OBJECTIVE: Whether ligation or reconstruction should be performed after radical resection of the tumor and carotid artery in patients with head and neck cancers invading the carotid artery (HNC-CA) has been controversial. This paper provides a review and meta-analysis of the efficacy of these 2 modalities. DATA SOURCES: PubMed, Cochrane, Web of Science, Scopus, and Ovid databases were searched through August 2023. REVIEW METHODS: Descriptive, graphical, tabular, and quantitative data were extracted. The statistical outcomes (risk difference, RD) were synthesized under a random-effects model. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. RESULTS: A total of 22 papers and 337 patients met the inclusion criteria for the literature review. Statistical analysis showed that the RD of overall survival (OS) rate at 1-year was 32% (95% confidence interval [CI]: 21%-42%) for ligation and 70% (95% CI: 65%-76%) for reconstruction (P < .05). The RD for OS rate at 2-year was 16% (95% CI: 7%-26%) for ligation and 39% (95% CI: 30%-47%) for reconstruction (P < .05). The RD for disease-free survival rate at 1-year was 27% (95% CI: 17%-38%) for ligation and 60% (95% CI: 51%-70%) for reconstruction (P < .05). There were no statistically significant differences (P > .05) between the 2 surgical modalities in terms of locoregional recurrence rate, carotid blowout rate, surgery-related complications rate, neurological complications rate, and perioperative mortality rate. CONCLUSION: This review demonstrates the significant advantage of carotid artery reconstruction surgery in short-term patient survival, thus making it a recommended option for HNC-CA patients undergoing radical surgery.
Bile acids play a vital role in modulating host metabolism, with chenodeoxycholic acid (CDCA) standing out as a primary bile acid that naturally activates farnesoid X receptor (FXR). In this study, we investigated the microbial transformations of CDCA by seven human intestinal fungal species. Our findings revealed that hydroxylation and dehydrogenation were the most prevalent metabolic pathways. Incubation of CDCA with Rhizopus microspores (PT2906) afforded eight undescribed compounds (6-13) alongside five known analogs (1-5) which were elucidated by HRESI-MS and NMR data. Notably, compounds 8, 12 and 13 exhibited an inhibitory effect on FXR in contrast to the FXR activation observed with CDCA in vitro assays. This study shone a light on the diverse transformations of CDCA by intestinal fungi, unveiling potential modulators of FXR activity with implications for host metabolism.
Owing to population growth and environmental pollution, freshwater aquaculture has been rapidly shrinking in recent years. Aquaculture in saline-alkaline waters is a crucial strategy to meet the increasing demand for aquatic products. The Chinese mitten crab is an important economic food in China, but the molecular mechanism by which it tolerates carbonate alkalinity (CA) in water remains unclear. Here, we found that enzyme activities of the tricarboxylic acid (TCA) cycle in the gills, such as citrate synthase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, and malate dehydrogenase, were markedly reduced under CA stress induced by 40 mM NaHCO3. Secondly, the TCA cycle in the gills is inhibited under acute CA stress, according to proteomic and metabolomic analyses. The expressions of six enzymes, namely aconitate hydratase, isocitrate dehydrogenase, 2-oxoglutarate dehydrogenase, dihydrolipoyl dehydrogenase, succinate-CoA ligase, and malate dehydrogenase, were downregulated, resulting in the accumulation of phosphoenolpyruvic acid, citric acid, cis-aconitate, and α-ketoglutaric acid. Finally, we testified that if the TCA cycle is disturbed by malonate, the survival rate increases in CA water. To our knowledge, this is the first study to show that the TCA cycle in the gills is inhibited under CA stress. Overall, the results provide new insights into the molecular mechanism of tolerance to saline-alkaline water in crabs, which helped us expand the area for freshwater aquaculture and comprehensively understand the physiological characteristics of crab migration.
Single-cell multiomic and exosome analyses are potent tools in various fields, such as cancer research, immunology, neuroscience, microbiology, and drug development. They facilitate the in-depth exploration of biological systems, providing insights into disease mechanisms and aiding in treatment. Single-cell isolation, which is crucial for single-cell analysis, ensures reliable cell isolation and quality control for further downstream analyses. Microfluidic chips are small lightweight systems that facilitate efficient and high-throughput single-cell isolation and real-time single-cell analysis on- or off-chip. Therefore, most current single-cell isolation and analysis technologies are based on the single-cell microfluidic technology. This review offers comprehensive guidance to researchers across different fields on the selection of appropriate microfluidic chip technologies for single-cell isolation and analysis. This review describes the design principles, separation mechanisms, chip characteristics, and cellular effects of various microfluidic chips available for single-cell isolation. Moreover, this review highlights the implications of using this technology for subsequent analyses, including single-cell multiomic and exosome analyses. Finally, the current challenges and future prospects of microfluidic chip technology are outlined for multiplex single-cell isolation and multiomic and exosome analyses.
The gut fungal community represents an essential element of human health, yet its functional and metabolic potential remains insufficiently elucidated, largely due to the limited availability of reference genomes. To address this gap, we presented the cultivated gut fungi (CGF) catalog, encompassing 760 fungal genomes derived from the feces of healthy individuals. This catalog comprises 206 species spanning 48 families, including 69 species previously unidentified. We explored the functional and metabolic attributes of the CGF species and utilized this catalog to construct a phylogenetic representation of the gut mycobiome by analyzing over 11,000 fecal metagenomes from Chinese and non-Chinese populations. Moreover, we identified significant common disease-related variations in gut mycobiome composition and corroborated the associations between fungal signatures and inflammatory bowel disease (IBD) through animal experimentation. These resources and findings substantially enrich our understanding of the biological diversity and disease relevance of the human gut mycobiome.
The burgeoning interest in the versatile hydrogel matrix, with its multifarious applications, has spurred extensive research in recent years. However, the implementation of chemically crosslinked gels on a large-scale has been hindered by their poor biosafety and excessive energy consumption. To address these challenges, this study focuses on harnessing physical methods to engineer novel composite hydrogels utilizing natural polysaccharides Salecan and whey protein isolate, obviating the need for structural modification or chemical crosslinking. The aim was to explore the rheological properties to understand their multiple behaviors. Various models, including Power-Law, Herschel-Bulkley, and Arrhenius, were also employed to compare and analyze rheological parameters. This study holds significance as it is the pioneering report on the hydrogels fabricated from Salecan/Whey protein isolate. These gels possess favorable attributes encompassing optimized elasticity, thermal-stability, enhanced injectability, and self-recovery, rendering them suitable for a multitude of applications in the realms of food and biomedicine.
