Hydrogenation of Furfural over Biomass-Based Electron-Deficient Co-NC Nanotube Catalyst.

The conversion of furfural to furfuryl alcohol is one of the most significant reactions from industrial-scale produced biomass platform molecules to value-added chemicals. In this work, biomass-based chitosan was used as both a carbon source and nitrogen source to synthesize nitrogen-doped carbon. With the addition of cobalt, the optimized 7.5Co-NC-900 catalyst had the largest surface area and the graphite nanotube structure with the least defects. It was employed for the hydrogenation of furfural to furfuryl alcohol and reached a nearly full conversion and an equivalent yield at 130 °C in 4 MPa initial H2. The structure-function relationship study indicated that the N could interact with the neighbor Co in this catalyst and formed an electron-deficient Co center which was in favor of the adsorption of furfural in the nanotube and had high catalytic activity. The interactions between Co and N stabilized the catalyst so that it could remain stable in five runs of catalytic reactions.

Comprehensive analysis of T-cell regulatory factors and tumor immune microenvironment in stomach adenocarcinoma.

BACKGROUND: Gastric cancer (GC) is one of the most prevalent malignant tumors worldwide and is associated with high morbidity and mortality rates. However, the specific biomarkers used to predict the postoperative prognosis of patients with gastric cancer remain unknown. Recent research has shown that the tumor microenvironment (TME) has an increasingly positive effect on anti-tumor activity. This study aims to build signatures to study the effect of certain genes on gastric cancer. METHODS: Expression profiles of 37 T cell-related genes and their TME characteristics were comprehensively analyzed. A risk signature was constructed and validated based on the screened T cell-related genes, and the roles of hub genes in GC were experimentally validated. RESULTS: A novel T cell-related gene signature was constructed based on CD5, ABCA8, SERPINE2, ESM1, SERPINA5, and NMU. The high-risk group indicated lower overall survival (OS), poorer immune efficacy, and higher drug resistance, with SERPINE2 promoting GC cell proliferation, according to experiments. SERPINE2 and CXCL12 were significantly correlated, indicating poor OS via the Youjiang cohort. CONCLUSIONS: This study identified T cell-related genes in patients with stomach adenocarcinoma (STAD) for prognosis estimation and proposed potential immunotherapeutic targets for STAD.

Micro-and nano-plastics induce kidney damage and suppression of innate immune function in zebrafish (Danio rerio) larvae.

Aquatic environments serve as critical repositories for pollutants and have significantly accumulated micro- and nanoplastics (MNPs) due to the extensive production and application of plastic products. While the disease resistance and immunity of fish are closely linked to the condition of their aquatic habitats, the specific effects of nanoplastics (NPs) and microplastics (MPs) within these environments on fish immune functions are still not fully understood. The present study utilized zebrafish (Danio rerio) embryos and larvae as model organisms to examine the impacts of polystyrene NPs (100 nm) and MPs (5 µm) on fish immune responses. Our findings reveal that NPs and MPs tend to accumulate on the surfaces of embryos and within the intestines of larvae, triggering oxidative stress and significantly increasing susceptibility to Edwardsiella piscicida infection in zebrafish larvae. Transmission electron microscopy examined that both NPs and MPs inflicted damage to the kidney, an essential immune organ, with NPs predominantly inducing endoplasmic reticulum stress and MPs causing lipid accumulation. Transcriptomic analysis further demonstrated that both NPs and MPs significantly suppress the expression of key innate immune pathways, notably the C-type lectin receptor signaling pathway and the cytosolic DNA-sensing pathway. Within these pathways, the immune factor interleukin-1 beta (il1b) was consistently downregulated in both exposure groups. Furthermore, exposure to E. piscicida resulted in restricted upregulation of il1b mRNA and protein levels, likely contributing to diminished disease resistance in zebrafish larvae exposed to MNPs. Our findings suggest that NPs and MPs similarly impair the innate immune function of zebrafish larvae and weaken their disease resistance, highlighting the significant environmental threat posed by these pollutants.

20(S)-Protopanaxadiol Exerts Antidepressive Effects in Chronic Corticosterone-Induced Rodent Animal Models as an Activator of Brain-Type Creatine Kinase.

20(S)-Protopanaxadiol (PPD) is one of the bioactive ingredients in ginseng and possesses neuroprotective properties. Brain-type creatine kinase (CK-BB) is an enzyme involved in brain energy homeostasis via the phosphocreatine-creatine kinase system. We previously identified PPD as directly bound to CK-BB and activated its activity in vitro. In this study, we explored the antidepressive effects of PPD that target CK-BB. First, we conducted time course studies on brain CK-BB, behaviors, and hippocampal structural plasticity responses to corticosterone (CORT) administration. Five weeks of CORT injection reduced CK-BB activity and protein levels and induced depression-like behaviors and hippocampal structural plasticity impairment. Next, a CK inhibitor and an adeno-associated virus-targeting CKB were used to diminish CK-BB activity or its expression in the brain. The loss of CK-BB in the brain led to depressive behaviors and morphological damage to spines in the hippocampus. Then, a polyclonal antibody against PPD was used to determine the distribution of PPD in the brain tissues. PPD was detected in the hippocampus and cortex and observed in astrocytes, neurons, and vascular endotheliocytes. Finally, different PPD doses were used in the chronic CORT-induced depression model. Treatment with a high dose of PPD significantly increased the activity and expression of CK-BB after long-term CORT injection. In addition, PPD alleviated the damage to depressive-like behaviors and structural plasticity induced by repeated CORT injection. Overall, our study revealed the critical role of CK-BB in mediating structural plasticity in CORT-induced depression and identified CK-BB as a therapeutic target for PPD, allowing us to treat stress-related mood disorders.

Metformin normalizes mitochondrial function to delay astrocyte senescence in a mouse model of Parkinson's disease through Mfn2-cGAS signaling.

BACKGROUND: Senescent astrocytes play crucial roles in age-associated neurodegenerative diseases, including Parkinson's disease (PD). Metformin, a drug widely used for treating diabetes, exerts longevity effects and neuroprotective activities. However, its effect on astrocyte senescence in PD remains to be defined. METHODS: Long culture-induced replicative senescence model and 1-methyl-4-phenylpyridinium/α-synuclein aggregate-induced premature senescence model, and a mouse model of PD were used to investigate the effect of metformin on astrocyte senescence in vivo and in vitro. Immunofluorescence staining and flow cytometric analyses were performed to evaluate the mitochondrial function. We stereotactically injected AAV carrying GFAP-promoter-cGAS-shRNA to mouse substantia nigra pars compacta regions to specifically reduce astrocytic cGAS expression to clarify the potential molecular mechanism by which metformin inhibited the astrocyte senescence in PD. RESULTS: We showed that metformin inhibited the astrocyte senescence in vitro and in PD mice. Mechanistically, metformin normalized mitochondrial function to reduce mitochondrial DNA release through mitofusin 2 (Mfn2), leading to inactivation of cGAS-STING, which delayed astrocyte senescence and prevented neurodegeneration. Mfn2 overexpression in astrocytes reversed the inhibitory role of metformin in cGAS-STING activation and astrocyte senescence. More importantly, metformin ameliorated dopamine neuron injury and behavioral deficits in mice by reducing the accumulation of senescent astrocytes via inhibition of astrocytic cGAS activation. Deletion of astrocytic cGAS abolished the suppressive effects of metformin on astrocyte senescence and neurodegeneration. CONCLUSIONS: This work reveals that metformin delays astrocyte senescence via inhibiting astrocytic Mfn2-cGAS activation and suggest that metformin is a promising therapeutic agent for age-associated neurodegenerative diseases.

Efficacy and safety of dabigatran and rivaroxaban in atrial fibrillation patients with impaired liver function: a multicenter retrospective cohort study.

BACKGROUND: The efficacy and safety of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) patients with impaired liver function (ILF) have not been sufficiently studied. The aim of this study was to evaluate the efficacy and safety of DOACs for stroke prevention in patients with AF and ILF. METHOD: This study was based on data from 15 centers in China, including 4,982 AF patients. The patients were divided into 2 subgroups based on their liver function status: patients with normal liver function (NLF)(n = 4213) and patients with ILF (n = 769). Logistic regression analysis was used to investigate the risk of total bleeding, major bleeding, thromboembolism, and all-cause deaths in AF patients with NLF and ILF after taking dabigatran or rivaroxaban, respectively. RESULTS: Among AF patients treated with dabigatran or rivaroxaban, patients with ILF were associated with significantly higher major bleeding, compared with NLF patients (aOR: 4.797; 95% CI: 2.224-10.256; P < 0.001). In patients with NLF, dabigatran (n = 2011) had considerably lower risk of total bleeding than rivaroxaban (n = 2202) (aOR: 1.23; 95% CI: 1.002-1.513; P = 0.049). In patients with ILF, dabigatran (n = 321) significantly favored lower risks of major bleeding compared with rivaroxaban(n = 448) (aOR: 5.484; 95% CI: 1.508-35.269; P = 0.026). CONCLUSION: After using dabigatran or rivaroxaban, patients with ILF had remarkably increased risk of major bleeding compared with patients with NLF. In AF patients with NLF, dabigatran had the distinct strength of significantly reduced risk of total bleeding compared with rivaroxaban. In patients with AF and ILF, dabigatran use was associated with lower risk for major bleeding compared with rivaroxaban.

Prediction of high-level fear of cancer recurrence in breast cancer survivors: An integrative approach utilizing random forest algorithm and visual nomogram.

PURPOSE: This study is the first attempt to use a combination of regression analysis and random forest algorithm to predict the risk factors for high-level fear of cancer recurrence and develop a predictive nomogram to guide clinicians and nurses in identifying high-risk populations for high-level fear of cancer recurrence. METHODS: After receiving various recruitment strategies, a total of 781 survivors who had undergone breast cancer resection within 5 years in four Grade-A hospitals in China were included. Besides demographic and clinical characteristics, variables were also selected from the perspectives of somatic, cognitive, psychological, social and economic factors, all of which were measured using a scale with high reliability and validity. This study established univariate regression analysis and random forest model to screen for risk factors for high-level fear of cancer recurrence. Based on the results of the multi-variable regression model, a nomogram was constructed to visualize risk prediction. RESULTS: Fatigue, social constraints, maladaptive cognitive emotion regulation strategies, meta-cognition and age were identified as risk factors. Based on the predictive model, a nomogram was constructed, and the area under the curve was 0.949, indicating strong discrimination and calibration. CONCLUSIONS: The integration of two models enhances the credibility of the prediction outcomes. The nomogram effectively transformed intricate regression equations into a visual representation, enhancing the readability and accessibility of the prediction model's results. It aids clinicians and nurses in swiftly and precisely identifying high-risk individuals for high-level fear of cancer recurrence, enabling the development of timely, predictable, and personalized intervention programs for high-risk patients.

Tissue-specific enhancer-gene maps from multimodal single-cell data identify causal disease alleles.

Translating genome-wide association study (GWAS) loci into causal variants and genes requires accurate cell-type-specific enhancer-gene maps from disease-relevant tissues. Building enhancer-gene maps is essential but challenging with current experimental methods in primary human tissues. Here we developed a nonparametric statistical method, SCENT (single-cell enhancer target gene mapping), that models association between enhancer chromatin accessibility and gene expression in single-cell or nucleus multimodal RNA sequencing and ATAC sequencing data. We applied SCENT to 9 multimodal datasets including >120,000 single cells or nuclei and created 23 cell-type-specific enhancer-gene maps. These maps were highly enriched for causal variants in expression quantitative loci and GWAS for 1,143 diseases and traits. We identified likely causal genes for both common and rare diseases and linked somatic mutation hotspots to target genes. We demonstrate that application of SCENT to multimodal data from disease-relevant human tissue enables the scalable construction of accurate cell-type-specific enhancer-gene maps, essential for defining noncoding variant function.

Single-Cell Sequencing Reveals MYOF-Enriched Monocyte/Macrophage Subcluster as a Favorable Prognostic Factor in Sepsis.

This research utilized single-cell RNA sequencing to map the immune cell landscape in sepsis, revealing 28 distinct cell clusters and categorizing them into nine major types. Delving into the monocyte/macrophage subclusters, 12 unique subclusters are identified and pathway enrichment analyses are conducted using KEGG and GO, discovering enriched pathways such as oxidative phosphorylation and antigen processing. Further GSVA and AUCell assessments show varied activation of interferon pathways, especially in subclusters 4 and 11. The clinical correlation analysis reveals genes significantly linked to survival outcomes. Additionally, cellular differentiation in these subclusters is explored. Building on these insights, the differential gene expression within these subclusters is specifically scrutinized, which reveal MYOF as a key gene with elevated expression levels in the survivor group. This finding is further supported by in-depth pathway enrichment analysis and the examination of cellular differentiation trajectories, where MYOF's role became evident in the context of immune response regulation and sepsis progression. Validating the role of the MYOF gene in sepsis, a dose-dependent response to LPS in THP-1 cells and C57 mice is observed. Finally, inter-cellular communications are analyzed, particularly focusing on the MYOF+Mono/Macro subcluster, which indicates a pivotal role in immune regulation and potential therapeutic targeting.

Social Frailty and Functional Status in Japanese Older Adults: The Mediating Role of Subjective Cognitive Function.

OBJECTIVE: This study aimed to explore the direct and indirect effects of social frailty on functional state trajectories mediated by subjective cognitive function in older adults. DESIGN: Longitudinal study. SETTING AND PARTICIPANTS: Overall, 514 adults aged ≥65 years living in a suburban area of central Japan were included in this study. METHODS: Five-item social frailty index (going out, visiting, feeling helpful, living alone, and talking to others), subjective cognitive function from the Kihon Checklist, and instrumental activities of daily living disability. Latent growth curve models were applied to examine the longitudinal relations among the variables. RESULTS: During the 6-year follow-up in latent growth curve models, the initial level of social frailty in older adults was negatively associated with that of functional status (ß = -0.53, P < .001), and the rate of change in social frailty was negatively associated with that in functional status (ß = -0.78, P < .001). In the mediation model, the indirect effect from the social frailty level to functional status level through subjective cognitive function level was significant (ß = -0.14, 95% CI -0.29, -0.09); the rates of change in subjective cognitive function mediated the relationship between those in social frailty and functional status (ß = -0.35, 95% CI -0.46, -0.25). CONCLUSIONS AND IMPLICATIONS: This study found that there is an association between social frailty and functional status in Japanese older adults. Subjective cognitive function mediated this relationship. Hence, additional research is required to investigate additional potential factors linking social frailty and functional status in order to gain a better understanding of the underlying mechanisms.

Concentrations, Sources and Health Risk Assessment of Polycyclic Aromatic Hydrocarbons in Chinese Herbal Medicines.

The determination and evaluation of 16 polycyclic aromatic hydrocarbons (PAHs) in seven Chinese herbal medicines (CHMs) were conducted through a rapid and straightforward extraction and purification method, coupled with GC-MS. A sample-based solid-phase extraction (SPE) pretreatment technique, incorporating isotopic internal standards, was employed for detecting various medicinal parts of CHMs. The assay exhibited linearity within the range of 5 to 500 ng/mL, with linear coefficients (R2) for PAHs exceeding 0.999. The recoveries of spiked standards ranged from 63.37% to 133.12%, with relative standard deviations (RSDs) ranging from 0.75% to 14.54%. The total PAH content varied from 176.906 to 1414.087 µg/kg. Among the 16 PAHs, phenanthrene (Phe) was consistently detected at the highest levels (47.045-168.640 µg/kg). Characteristic ratio analysis indicated that oil, coal, and biomass combustion were the primary sources of PAHs in CHMs. The health risk associated with CHMs was assessed using the lifetime carcinogenic risk approach, revealing potential health risks from the consumption of honeysuckle, while the health risks of consuming Lycium chinense berries were deemed negligible. For the other five CHMs (glycyrrhizae, Coix lacryma, ginseng, lotus seed, seed of Sterculia lychnophora), the health risk from consumption fell within acceptable ranges. Furthermore, sensitivity analyses utilizing Monte Carlo exposure assessment methods identified PAH levels in CHMs as health risk sensitizers. It is crucial to recognize that the consumption of herbal medicines is not a continuous process but entails potential health risks. Hence, the monitoring and risk assessment of PAH residues in CHMs demand careful attention.

Facile superhydrophobic modification on HPMC film using polydimethylsiloxane and starch granule coatings.

The excessive water sensitivity of hydroxypropyl methylcellulose (HPMC) films prevent them from being used extensively. In order to overcome this limitation, superhydrophobic HPMC films were meticulously crafted through the utilization of a composite of polydimethylsiloxane (PDMS) and ball-milled rice starch, corn starch, or potato starch (RS/CS/PS) for the coating process. Initially possessing hydrophilic properties, the HPMC Film (CA = 49.3 ± 1.8°) underwent a transformative hydrophobic conversion upon the application of PDMS, resulting in a static contact angle measuring up to 103.4 ± 2.0°. Notably, the synergistic combination of PDMS-coated HPMC with ball-milled starch demonstrated exceptional superhydrophobic attributes. Particularly, the treated HPMC-based film, specifically the HP-CS-2 h film, showcased an impressive contact angle of 170.5° alongside a minimal sliding angle of 5.2°. The impact of diverse starch types and the ball milling treatment on the PDMS/starch coatings and HPMC film was thoroughly examined using scanning electron microscopy (SEM), wide-angle X-ray diffraction (WAXS), and particle size analysis. These studies demonstrated that the low surface energy and roughness required for the creation of superhydrophobic HPMC-based films were imparted by the hierarchical structure formed by the application of PDMS/ball-milled starch. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Polydimethylsiloxane (PubChem CID: 24764); Hydroxypropyl methylcellulose (PubChem CID: 671); Ethyl acetate (PubChem CID: 8857).

Longitudinal assessment of the relationship between frailty and social relationships among Japanese older adults: a random intercept cross-lagged panel model.

OBJECTIVES: This study aimed to explore the bidirectional association between frailty and social relationships in older adults while distinguishing between interpersonal and intrapersonal effects. METHODS: A prospective cohort study of community-dwelling older adults was conducted in Japan in three waves spanning six years with follow-ups in every three years. Random intercept cross-lagged panel model was used to explore temporal associations between frailty and social relationships. RESULTS: Data for 520 participants (mean age 73.02 [SD 6.38] years, 56.7% women) were analyzed. Across individuals, frailty was associated with social relationships (ß = -0.514, p < 0.001). At the interpersonal level, frailty was cross-sectionally associated with social relationships separately at T1(ß = -0.389, p < 0.01), T2 (ß = -0.343, p < 0.001) and T3 (ß = -0.273, p < 0.05). Moreover, social relationships were associated with subsequent increases in symptoms of frailty in all measurement waves (ß = -0.332, p < 0.001; ß = -0.169, p < 0.01) and vice versa (ß = -0.149, p < 0.05; ß = -0.292, p < 0.001). CONCLUSIONS: The results suggest that frailty was associated with lower levels of social relationships. Frailty improvement programs can be combined with interventions to enhance social relationships, which will be beneficial in preventing frailty. The results emphasize the importance of combining clinical treatments of frailty with interventions to improve social relationships.

Discovery and validation of COX2 as a target of flavonoids in Apocyni Veneti Folium: Implications for the treatment of liver injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Apocyni Veneti Folium (AVF), a popular traditional Chinese medicine (TCM), is known for its effects in soothing the liver and nerves and eliminating heat and water. It is relevant from an ethnopharmacological perspective. Pharmacological research has confirmed its benefits on antihypertension, antihyperlipidemia, antidepression, liver protection, immune system boosting, antiaging, and diabetic vascular lesions. Previous studies have shown that flavonoids, the active ingredients, have a hepatoprotective effect. However, the exact mechanism has not been clarified. AIM OF THE STUDY: This study aimed to identify the active flavonoids in AVF and their corresponding targets for liver injury. Multiple methods were introduced to confirm the targets. MATERIAL AND METHODS: AVF compounds were analyzed using liquid chromatography-mass spectrometry (LC-MS). Then, network pharmacology was utilized to screen potential hepatoprotection targets of the compounds. An enzyme activity assay was performed to determine the effect of the compounds on the targets. Biolayer interferometry (BLI) was applied to confirm the direct interaction between the compounds and the targets. RESULTS: A total of 71 compounds were identified by LC-MS and 19 compounds and 112 shared targets were screened using network pharmacology. These common targets were primarily involved in the TNF signaling pathway, cancer pathways, hepatitis B, drug responses, and negative regulation of the apoptotic process. Flavonoids were the primary pharmacological substance basis of AVF. The cyclooxygenase 2 (COX2) protein was one of the direct targets of flavonoids in AVF. The enzyme activity assay and BLI-based intermolecular interactions demonstrated that the compounds astragalin, isoquercitrin, and hyperoside exhibited stronger inhibition of enzyme activity and a higher affinity with COX2 compared to epigallocatechin, quercetin, and catechin. CONCLUSIONS: COX2 was preliminarily identified as a target of flavonoids, and the mechanism of the hepatoprotective effect of AVF might be linked to flavonoids inhibiting the activity of COX2. The findings can establish the foundation for future research on the traditional hepatoprotective effect of AVF on the liver and for clinical studies on liver disorders.

Association of Interleukin-17A and Interleukin-17F Gene Polymorphisms with Atopic Dermatitis in Chinese Children.

Background: Atopic dermatitis (AD) is a chronic, recurrent inflammatory disease associated with an unbalanced immune response in the upper layers of the skin tissue, mostly starting in childhood. As important factors in gene expression regulation, polymorphisms in interleukin (IL)-17A and IL-17F may be associated with the susceptibility and severity of AD. Methods: Blood samples and clinical information were obtained from 132 patients with AD and 100 healthy children. Using multiplex polymerase chain reaction and next-generation sequencing, five potential single-nucleotide polymorphisms (SNPs) of IL-17A and IL-17F were genotyped in all participants. The relationship between SNPs and susceptibility to or severity of AD was examined by analyzing haplotypes and genetic models. Results: The IL-17A rs3819025 polymorphism was substantially associated with higher AD risk in both the allele model (p = 0.03; odds ratio [OR] = 1.76; confidence interval [CI]: 1.05-2.95) and the dominant model (p = 0.04, OR = 1.85; CI: 1.03-3.33). There was no correlation between AD susceptibility and the IL-17A (rs2275913 and rs4711998) or IL-17F (rs763780 and rs12203736) SNPs (all p > 0.05). Additionally, the five IL-17A and IL-17F SNPs did not significantly differ across the mild-to-moderate and severe subgroups (all p > 0.05). Conclusions: The IL-17A/rs3819025 polymorphism was linked to the development of AD, whereas the IL-17F polymorphism was unrelated to the susceptibility to and severity of AD. The IL-17A polymorphism may provide valuable information to speculate on the susceptibility to AD in Chinese Han children.

Immune-restoring CAR-T cells display antitumor activity and reverse immunosuppressive TME in a humanized ccRCC mouse model.

One of the major barriers that have restricted successful use of chimeric antigen receptor (CAR) T cells in the treatment of solid tumors is an unfavorable tumor microenvironment (TME). We engineered CAR-T cells targeting carbonic anhydrase IX (CAIX) to secrete anti-PD-L1 monoclonal antibody (mAb), termed immune-restoring (IR) CAR G36-PDL1. We tested CAR-T cells in a humanized clear cell renal cell carcinoma (ccRCC) orthotopic mouse model with reconstituted human leukocyte antigen (HLA) partially matched human leukocytes derived from fetal CD34+ hematopoietic stem cells (HSCs) and bearing human ccRCC skrc-59 cells under the kidney capsule. G36-PDL1 CAR-T cells, haploidentical to the tumor cells, had a potent antitumor effect compared to those without immune-restoring effect. Analysis of the TME revealed that G36-PDL1 CAR-T cells restored active antitumor immunity by promoting tumor-killing cytotoxicity, reducing immunosuppressive cell components such as M2 macrophages and exhausted CD8+ T cells, and enhancing T follicular helper (Tfh)-B cell crosstalk.

Proteome-wide identification and functional analysis of ubiquitinated proteins in Hepa1-6 cells by knockdown of E3 ubiquitin ligase SIAH1.

Background: Hepatocellular carcinoma (HCC) is an aggressive malignancy that poses a serious threat to human life. The conventional therapies for HCC cannot substantially improve overall survival (OS), disease duration, and prognosis. Therefore, it is important to study the underlying mechanism of HCC and seek better methods for HCC prevention and treatment. Ubiquitination is a post-translational modification that modulates great cellular function by cooperating with E1, E2, and E3 ligases. Yet, the ubiquitination and lysine residues in HCC are still elusive. Seven in absentia homolog 1 (SIAH1), as an important E3 ubiquitin ligase, regulates ubiquitin-mediated proteolysis to function as a tumor suppressor in HCC. In the present study, we downregulated SIAH1 in the mouse HCC cell line Hepa1-6 and studied its function by using proteome-wide identification. Methods: SIAH1 was knocked down by SIAH1 short hairpin RNA (shRNA) in mouse HCC cell line Hepa1-6 cells, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was conducted to analyze the ubiquitinated proteins. Functional analysis was performed using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment. Results: The systematic profiling showed a total of 550 differently expressed proteins (DEPs), including 263 upregulated DEPs and 287 downregulated DEPs. Considering the amino acid sequences around the modified lysine residues, seven proteins were identified as conserved ubiquitination motifs in the peptides. The ubiquitinated proteins were mainly distributed in the cytoplasm, nucleus, and plasma membrane. Functional analysis suggested that the ubiquitinated proteins were mostly enriched in the nucleus, cytoplasm, and extracellular space; in addition, the ubiquitinated proteins were mostly attributed to the protein binding, and disease. The ubiquitinated proteins modulate HCC by mapping lysine modification sites. Conclusions: The use of high-throughput characterization to identify novel and specific targets associated with SIAH1 is of great significance in terms of functional weight. The results obtained in this paper from the analysis of proteomic data provided novel insights into ubiquitination regulation in HCC, which pave the way for further research and mechanism discovery of HCC.

Donor engineering of a benzothiadiazole-based D-A-D-type molecular semiconductor for perovskite solar cells: a theoretical study.

Due to the easy formation of compact molecular packing arrangements and the favorable photophysical and electrochemical properties, donor-acceptor-donor (D-A-D)-type small molecule hole-transporting materials (HTMs) have been widely synthesized and researched to improve the efficiency and stability of perovskite solar cells (PSCs). The main approach in recent experiments has been to seek good acceptors, whereas the influence of the electron-donating units has been less reported. In this work, six new benzothiadiazole-based D-A-D-type HTMs are tailored by employing the ethyl-substituted phenoxazine (POZ), phenothiazine (PTZ) and carbazole (CZ) as the donors. To obtain an elementary understanding of new HTMs, the electronic, optical, hole-transporting and interfacial properties are simulated with quantum chemistry methods. The results indicate that all tailored HTMs exhibit suitable energy alignment compared with the band structures of the perovskite, and the continuous highest occupied molecular orbital (HOMO) levels will be helpful for interfacial energy regulation. In comparison with the YN1, the maximum absorption wavelengths of the newly designed HTMs are red-shifted due to the decreased excitation energies from the ground-state to the first singlet excited-state. Importantly, the hole mobilities of all designed HTMs are distinctly higher than the referenced YN1, which is contributed by the better planarity of the molecular skeleton and the easier orbital overlapping between adjacent molecules. The interfacial simulations manifest that the FAPbI3/SM37 system displays a more stable adsorption configuration and greater charge redistributions at the interface compared to YN1, which further promotes the separation of photogenerated electron-hole pairs. Moreover, larger Stokes shifts and better solubility are also acquired for the new HTMs. In summary, our calculations not only propose several potential highly efficient HTMs, but also provide useful insights at the atomic level for the experimental synthesis of new D-A-D-type HTMs.

Preparation and characterization of peach gum/chitosan polyelectrolyte composite films with dual cross-linking networks for antibacterial packaging.

Peach gum (PG) is a valuable polymeric feedstock for developing eco-friendly, bio-safe, and functional materials. However, PG has limited use in food packaging due to its inferior mechanical and antibacterial properties. To overcome these limitations, we created a dual cross-linked network by introducing chitosan (CS) and glycerol to the PG matrix. Our research discovered that incorporating CS into the PG matrix significantly improved its Young's modulus, from 277.62 to 925.89 MPa, and its tensile strength from 5.96 to 39.94 MPa. Furthermore, the inclusion of glycerol greatly increased the elongation. These enhancements were attributed to the ionic and hydrogen-bonding interactions between the two biopolymers. Additionally, the composite films exhibited strong antibacterial effects, reducing the total number of colonies by 99.2 % and 99.9 % against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), respectively. The incorporation of CS resulted in more amorphous films, enhancing their stiffness, flexibility, and barrier properties. To assess the practical application of PG/CS composite films, we conducted a comparative analysis between non-packaged strawberries and strawberries packaged with these films. The results demonstrated that the composite polyelectrolyte film extended the shelf life of strawberries better than the non-packaged fruits.

Laparoscopic hepatectomy for hepatocellular carcinoma in patients with clinically significant portal hypertension: a systematic review and meta-analysis.

OBJECTIVE: To compare the effects of laparoscopic hepatectomy (LH) on the short-term and long-term outcomes in hepatocellular carcinoma (HCC) patients with and without clinically significant portal hypertension (CSPH). METHODS: A systematic literature search of the PubMed, EMBASE, and Cochrane databases was performed for articles published from inception to March 1, 2023. Meta-analysis of surgical and oncological outcomes was performed using a random effects model. Data were summarized as mean difference and risk ratio with 95% confidence intervals. RESULTS: Five cohort studies with a total of 310 HCC patients were included (CSPH 143; Non-CSPH 167). In terms of surgical outcomes, estimated blood loss and the length of hospital stay were significantly lower in the Non-CSPH group than in the CSPH group. There were no significant differences between the two groups regarding other surgical outcomes, including the operative time, ratio of conversion to open surgery, and overall complication rate. In addition, there were also no significant differences between the two groups regarding the oncological outcomes, such as 1-, 3-, and 5-year overall survival. CONCLUSIONS: HCC patients with and without CSPH who underwent LH had comparable surgical and oncological outcomes. LH is a safe and effective treatment for HCC patients with CSPH under the premise of rational screening of patients.