Adjuvant Transarterial Chemoembolization With Sorafenib for Portal Vein Tumor Thrombus: A Randomized Clinical Trial.

Importance: Certain patients with hepatocellular carcinoma with portal vein tumor thrombus could benefit from surgical resection, and postoperative adjuvant therapy may lower the incidence of tumor recurrence. Objective: To compare the efficacy and safety of sorafenib plus transarterial chemoembolization vs sorafenib alone as postoperative adjuvant therapy for patients with hepatocellular carcinoma with portal vein tumor thrombus. Design, Setting, and Participants: This was a phase 3, multicenter, randomized clinical trial conducted in 5 hospitals in China. A total of 158 patients were enrolled and randomized from October 2019 to March 2022, with a median follow-up of 28.4 months. Portal vein tumor thrombus was graded by the Cheng classification. Eligible patients with hepatocellular carcinoma with Cheng grade I to III portal vein tumor thrombus (ie, involving segmental or sectoral branches, right- or left-side branch, or main trunk of portal vein) were included. Interventions: Patients were randomly assigned 1:1 to receive transarterial chemoembolization with sorafenib or sorafenib alone as postoperative adjuvant therapy. Sorafenib treatment was started within 3 days after randomization, with an initial dose of 400 mg orally twice a day. In the transarterial chemoembolization with sorafenib group, transarterial chemoembolization was performed 1 day after the first administration of sorafenib. Main Outcomes and Measures: The primary end point was recurrence-free survival. Efficacy was assessed in the intention-to-treat population and safety was assessed in patients who received at least 1 dose of study treatment. Results: Of 158 patients included, the median (IQR) age was 54 (43-61) years, and 140 (88.6%) patients were male. The median (IQR) recurrence-free survival was significantly longer in the transarterial chemoembolization with sorafenib group (16.8 [12.0-NA] vs 12.6 [7.8-18.1] months; hazard ratio [HR], 0.57; 95% CI, 0.39-0.83; P = .002). The median (IQR) overall survival was also significantly longer with transarterial chemoembolization with sorafenib than with sorafenib alone (30.4 [20.6-NA] vs 22.5 [15.4-NA] months; HR, 0.57; 95% CI, 0.36-0.91; P = .02). The most common grade 3/4 adverse event was hand-foot syndrome (23 of 79 patients in the transarterial chemoembolization with sorafenib group [29.1%] vs 24 of 79 patients in the sorafenib alone group [30.4%]). There were no treatment-related deaths in either group. The transarterial chemoembolization with sorafenib group did not show additional toxicity compared with the sorafenib monotherapy group. Conclusion and Relevance: In this study, the combination of sorafenib and transarterial chemoembolization as postoperative adjuvant therapy in patients with hepatocellular carcinoma with portal vein tumor thrombus resulted in longer recurrence-free survival and overall survival than sorafenib alone and was well tolerated. Trial Registration: ClinicalTrials.gov Identifier: NCT04143191.

The Physiological Response of Apricot Flowers to Low-Temperature Stress.

The growth and development of apricot flower organs are severely impacted by spring frosts. To better understand this process, apricot flowers were exposed to temperatures ranging from 0 °C to -8 °C, including a control at 18 °C, in artificial incubators to mimic diverse low-temperature environments. We aimed to examine their physiological reactions to cold stress, with an emphasis on changes in phenotype, membrane stability, osmotic substance levels, and antioxidant enzyme performance. Results reveal that cold stress induces significant browning and cellular damage, with a sharp increase in browning rate and membrane permeability below -5 °C. Soluble sugars and proteins initially rise as osmoprotectants, but their content decreases at lower temperatures. Proline content consistently increases, suggesting a protective role. Antioxidant enzyme activities, including catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and ascorbate peroxidase (APX), exhibit a complex pattern, with initial increases followed by declines at more severe cold conditions. Correlation and principal component analyses highlight the interplay between these responses, indicating a multifaceted adaptation strategy. The findings contribute to the understanding of apricot cold tolerance and inform breeding efforts for improved crop resilience.

[Determination of adenosine content in heart tissue by ultra performance liquid chromatography-triple quadrupole mass spectrometry].

A method based on ultra performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-MS/MS) was developed and validated for the rapid and accurate determination of adenosine (Ado) in cardiac tissues with high sensitivity and specificity. The samples were dissolved in 1 mL of ultrapure water containing 10 µmol/L 2-hydroxy-3-nonyladenine hydrochloride (EHNA) as a stabilizer, ground at low temperature for 2 min, and then ultrasonically extracted at 60 Hz in an ice-water bath for 40 min. Methanol and 5 mmol/L ammonium acetate solution were used as the mobile phases under a flow rate of 0.4 mL/min, a column temperature of 40 ℃ and an injection volume of 3 µL. The Ado in cardiac tissue was qualitatively and quantitatively analyzed by electrospray ionization (ESI) positive-ion-switching in multiple reaction monitoring (MRM) mode. A solvent standard curve and the external standard method were used for the accurate quantification of Ado. The results showed that the matrix effect of Ado in cardiac tissue was very low. A good linear relationship was obtained in the range of 0.1-160 ng/mL, and the correlation coefficient (r2) was 0.9930. The limits of detection (LOD) and quantification (LOQ) were 0.03 and 0.1 ng/mL, respectively. The spiked recoveries of Ado in murine cardiac tissue were 113.6%, 96.3%, and 102.9% at three spiked levels of low, medium, and high, respectively. The intra-day repeatability (RSDs) were 1.7%-8.4%, and the inter-day reproducibility (RSDs) were 2.6%-7.4%. Based on the correlation and consistency results, a positive bias was observed between the proposed UPLC-MS/MS method and the double-antibody sandwich method. Moreover, the Ado contents detected by these two methods were significantly positively correlated (P<0.0001). Cardiac tissue samples were collected from 17 mice and 17 rats and detected in our laboratory. The content ranges of Ado in the cardiac tissues of mice and rats determined by the developed UPLC-MS/MS method were 3.25-8.78 mg/kg and 10.24-15.19 mg/kg, respectively (average adenosine contents: 5.37 and 12.60 mg/kg, respectively). The developed method is simple, accurate, sensitive, and it is suitable for the determination of Ado in cardiac tissues. It also provides important technical support for cardiac clinical research and disease diagnosis.

Salvianolic acid C attenuates cerebral ischemic injury through inhibiting neuroinflammation via the TLR4-TREM1-NF-κB pathway.

BACKGROUND: Stroke is a leading cause of mortality and disability with ischemic stroke being the most common type of stroke. Salvianolic acid C (SalC), a polyphenolic compound found in Salviae Miltiorrhizae Radix et Rhizoma, has demonstrated therapeutic potential in the recovery phase of ischemic stroke. However, its pharmacological effects and underlying mechanisms during the early stages of ischemic stroke remain unclear. This study aimed to examine the potential mechanism of action of SalC during the early phase of ischemic stroke using network pharmacology strategies and RNA sequencing analysis. METHODS: SalC effects on infarct volume, neurological deficits, and histopathological changes were assessed in a mouse model of transient middle cerebral artery occlusion (tMCAO). By integrating RNA sequencing data with a cerebral vascular disease (CVD)-related gene database, a cerebral ischemic disease (CID) network containing dysregulated genes from the tMCAO model was constructed. Network analysis algorithms were applied to evaluate the key nodes within the CID network. In vivo and in vitro validation of crucial targets within the identified pathways was conducted. RESULTS: SalC treatment significantly reduced infarct volume, improved neurological deficits, and reversed pathological changes in the tMCAO mouse model. The integration of RNA sequencing data revealed an 80% gene reversion rate induced by SalC within the CID network. Among the reverted genes, 53.1% exhibited reversion rates exceeding 50%, emphasizing the comprehensive rebalancing effect of SalC within the CID network. Neuroinflammatory-related pathways regulated by SalC, including the toll-like-receptor 4 (TLR4)- triggering receptor expressed on myeloid cells 1 (TREM1)-nuclear factor kappa B (NF-κB) pathway, were identified. Further in vivo and in vitro experiments confirmed that TLR4-TREM1-NF-κB pathway was down-regulated by SalC in microglia, which was essential for its anti-inflammatory effect on ischemic stroke. CONCLUSIONS: SalC attenuated cerebral ischemic injury by inhibiting neuroinflammation mediated by microglia, primarily through the TLR4-TREM1-NF-κB pathway. These findings provide valuable insights into the potential therapeutic benefits of SalC in ischemic stroke.

Berkeley Open Extended Reality Recordings 2023 (BOXRR-23): 4.7 Million Motion Capture Recordings from 105,000 XR Users.

Extended reality (XR) devices such as the Meta Quest and Apple Vision Pro have seen a recent surge in attention, with motion tracking "telemetry" data lying at the core of nearly all XR and metaverse experiences. Researchers are just beginning to understand the implications of this data for security, privacy, usability, and more, but currently lack large-scale human motion datasets to study. The BOXRR-23 dataset contains 4,717,215 motion capture recordings, voluntarily submitted by 105,852 XR device users from over 50 countries. BOXRR-23 is over 200 times larger than the largest existing motion capture research dataset and uses a new, highly efficient and purpose-built XR Open Recording (XROR) file format.

The bioremediation of the typical persistent organic pollutants (POPs) by microalgae-bacteria consortia: A systematic review.

With industrialisation and the rapidly growing agricultural demand, many organic compounds have been leaked into the environment, causing serious damage to the biosphere. Persistent organic pollutants (POPs) are a type of toxic chemicals that are resistant to degradation through normal chemical, biological or photolytic approaches. With their stable chemical structures, POPs can be accumulated in the environment, and transported through wind and water, causing global environmental issues. Many researches have been conducted to remediate POPs contamination using various kinds of biological methods, and significant results have been seen. Microalgae-bacteria consortium is a newly developed concept for biological technology in contamination treatment, with the synergetic effects between microalgae and bacteria, their potential for pollutants degradation can be further released. In this review, two types of POPs (polychlorinated biphenyls and polycyclic aromatic hydrocarbons) are selected as the targeted pollutants to give a systematic analysis of the biodegradation through microalgae and bacteria, including the species selection, the identification of dominant enzymes, as well as the real application performance of the consortia. In the end, some outlooks and suggestions are given to further guide the development of applying microalgae-bacteria consortia in remediating POPs contamination. In general, the coculturing of microalgae and bacteria is a novel and efficient way to fulfil the advanced treatment of POPs in soil or liquid phase, and both monooxygenase and dioxygenase belonging to oxygenase play a vital role in the biodegradation of PCBs and PAHs. This review provides a general guide in the future investigation of biological treatment of POPs.

Transfer learning empowers accurate pharmacokinetics prediction of small samples.

Accurate assessment of pharmacokinetic (PK) properties is crucial for selecting optimal candidates and avoiding downstream failures. Transfer learning is an innovative machine learning approach enabling high-throughput prediction with limited data. Recently, transfer learning methods showed promise in predicting ADME/PK parameters. Given the prolific growth of research on transfer learning for PK prediction, a comprehensive review of its advantages and challenges is imperative. This study explores the fundamentals, classifications, toolkits and applications of various transfer learning techniques for PK prediction, demonstrating their utility through three practical case studies. This work will serve as a reference for drug design researchers.

Screening and dietary exposure assessment of T-2 toxin and its modified forms in commercial cereals and cereal-based products in Shanghai.

A reliable and sensitive UPLC-MS/MS method coupled with HLB-SPE was developed for simultaneous determination of T-2 and its modified forms (HT-2, NEO, T-2-triol, T-2-tetraol, T-2-3G, and HT-2-3G) in cereals and cereal-based products. Acceptable linearity (R2 ≥ 0.99), limits of quantitation (0.5-10.0 µg/kg), intra-day precision (RSD < 12.8 %), inter-day precision (RSD ≤ 15.8 %), and recovery (76.8 %-115.2 %) were obtained for all analytes in all matrices investigated. 107 commercial foodstuffs were analyzed, and T-2 was detected in 29.0 % of maize and maize flour samples (0.51 to 56.61 µg/kg) and in 10-33.3 % of wheat flour and barley samples (1.27 to 78.51 µg/kg). Moreover, 66.7 % of the positive samples were simultaneously contaminated with two or more T-2 forms. The possible health risk related to T-2 and its modified forms in cereals and cereal-based products was evaluated using a probabilistic dietary exposure assessment. The 95th percentile dietary exposure values of the sum of T-2 forms ranged from 0.16 to 1.70 ng/kg b.w./day for lower bound (LB), and 0.17 to 7.59 ng/kg b.w./day for upper bound (UB). Results strongly suggested that the presence of T-2 and its modified forms in cereals and cereal-based products warrants greater attention and investigation, although probabilistic dietary exposure values currently remain below the tolerable daily intake (TDI) value of 20 ng/kg b.w./day.

Atezolizumab Plus Bevacizumab Combined with Transarterial Embolization Plus Hepatic Arterial Infusion Chemotherapy for Unresectable Hepatocellular Carcinoma with a Diameter >8 Cm: A Retrospective Study.

Purpose: Local in combination with systemic therapy might be an option for patients with advanced unresectable hepatocellular carcinoma (uHCC). This study examined the clinical benefits and adverse events (AEs) of first-line transarterial embolization (TAE) and hepatic arterial infusion chemotherapy (HAIC) combined with atezolizumab (Atezo) and bevacizumab (Bev) in patients with uHCC of a diameter larger than 8 cm. Patients and methods: This retrospective study included patients with uHCC of a diameter larger than 8 cm who were treated with first-line Atezo-Bev and TAE+HAIC at the First Affiliated Hospital of Sun Yat-Sen University between September 30, 2019, and September 30, 2022. Progression-free survival (PFS), overall survival (OS), tumor response according to mRECIST, and AEs were analyzed. Multivariable Cox analyses were performed to examine the factors associated with PFS. Results: Thirty patients were included. The objective response rate (ORR) was 74.4% (95% confidence interval [CI], 59.3%-89.5%), and the disease control rate (DCR) was 93.3% (95% CI, 85.4%-98.6%). The median follow-up was 11.4 (inter-quartile range [IQR], 5.5-17.9) months. The median PFS was 6.8 (95% CI, 2.6-11.1) months. The 3-, 6-, 9-, and 12-month survival rates were 86.2%, 82.5%, 68.6%, and 60%, respectively. The median OS was not estimated. Extrahepatic metastasis was independently associated with PFS (hazard ratio [HR]=3.468, 95% CI, 1.001-12.023). The most common AEs were fever (46.7%). Grade 4 AEs occurred one time as hematemesis but no 5 AEs were observed. Conclusion: Atezo-Bev combined with TAE and HAIC might benefit patients with uHCC of a diameter larger than 8 cm, with manageable AEs.

Single-cell transcriptomic analysis reveals tumor cell heterogeneity and immune microenvironment features of pituitary neuroendocrine tumors.

BACKGROUND: Pituitary neuroendocrine tumors (PitNETs) are one of the most common types of intracranial tumors. Currently, the cellular characteristics of normal pituitary and various other types of PitNETs are still not completely understood. METHODS: We performed single-cell RNA sequencing (scRNA-seq) on 4 normal samples and 24 PitNET samples for comprehensive bioinformatics analysis. Findings regarding the function of PBK in the aggressive tumor cells were validated by siRNA knockdown, overexpression, and transwell experiments. RESULTS: We first constructed a reference cell atlas of the human pituitary. Subsequent scRNA-seq analysis of PitNET samples, representing major tumor subtypes, shed light on the intrinsic cellular heterogeneities of the tumor cells and tumor microenvironment (TME). We found that the expression of hormone-encoding genes defined the major variations of the PIT1-lineage tumor cell transcriptomic heterogeneities. A sub-population of TPIT-lineage tumor cells highly expressing GZMK suggested a novel subtype of corticotroph tumors. In immune cells, we found two clusters of tumor-associated macrophages, which were both highly enriched in PitNETs but with distinct functional characteristics. In PitNETs, the stress response pathway was significantly activated in T cells. While a majority of these tumors are benign, our study unveils a common existence of aggressive tumor cells in the studied samples, which highly express a set of malignant signature genes. The following functional experiments confirmed the oncogenic role of selected up-regulated genes. The over-expression of PBK could promote both tumor cell proliferation and migration, and it was also significantly associated with poor prognosis in PitNET patients. CONCLUSIONS: Our data and analysis manifested the basic cell types in the normal pituitary and inherent heterogeneity of PitNETs, identified several features of the tumor immune microenvironments, and found a novel epithelial cell sub-population with aggressive signatures across all the studied cases.

scCancer2: data-driven in-depth annotations of the tumor microenvironment at single-level resolution.

SUMMARY: Single-cell RNA-seq (scRNA-seq) is a powerful technique for decoding the complex cellular compositions in the tumor microenvironment (TME). As previous studies have defined many meaningful cell subtypes in several tumor types, there is a great need to computationally transfer these labels to new datasets. Also, different studies used different approaches or criteria to define the cell subtypes for the same major cell lineages. The relationships between the cell subtypes defined in different studies should be carefully evaluated. In this updated package scCancer2, designed for integrative tumor scRNA-seq data analysis, we developed a supervised machine learning framework to annotate TME cells with annotated cell subtypes from 15 scRNA-seq datasets with 594 samples in total. Based on the trained classifiers, we quantitatively constructed the similarity maps between the cell subtypes defined in different references by testing on all the 15 datasets. Secondly, to improve the identification of malignant cells, we designed a classifier by integrating large-scale pan-cancer TCGA bulk gene expression datasets and scRNA-seq datasets (10 cancer types, 175 samples, 663 857 cells). This classifier shows robust performances when no internal confidential reference cells are available. Thirdly, scCancer2 integrated a module to process the spatial transcriptomic data and analyze the spatial features of TME. AVAILABILITY AND IMPLEMENTATION: The package and user documentation are available at http://lifeome.net/software/sccancer2/ and https://doi.org/10.5281/zenodo.10477296.

Quantitative Parameters of Contrast-Enhanced Ultrasound Predicting the Response to Combined Immune Checkpoint Inhibitor and Anti-angiogenesis Therapies for Unresectable Hepatocellular Carcinoma.

OBJECTIVE: The aim of the work described here was to explore the value of contrast-enhanced ultrasound (CEUS) quantitative parameters in predicting the response of combined immune checkpoint inhibitor (ICI) and anti-angiogenesis therapies for unresectable hepatocellular carcinoma (HCC). METHODS: Sixty-six HCC patients who underwent combined ICI and anti-angiogenesis therapies were prospectively enrolled. A CEUS examination was performed at baseline, and tumor perfusion parameters were obtained with perfusion quantification software. The differences in CEUS quantitative parameters between the responder and non-responder groups were compared, and the correlations between CEUS parameters and progression-free survival (PFS) was evaluated. RESULTS: The objective response rate (ORR) was 21.2%. The values of rising time (RT) ratio, time to peak ratio, fall time ratio, peak enhancement ratio, wash-in rate ratio, wash-in perfusion index ratio and wash-out rate ratio differed significantly differed between the responder and non-responder groups (all p values < 0.05). Multivariable logistic regression analysis revealed that the RT ratio was the only independent factor associated with the ORR (odds ratio = 0.007, 95% confidence interval: 0.000-0.307, p = 0.010). The median RT ratios of the responder and non-responder groups were 36.9 and 58.9, respectively (p = 0.006). The appropriate cutoff point of the RT ratio was 80.1, determined with the X-tile program. Survival analysis indicated high PFS for the patients with a lower RT ratio (high RT ratio vs. low RT ratio = 4.4 mo vs. not reached, p = 0.001). CONCLUSION: CEUS quantitative parameters may predict the efficacy of ICI and anti-angiogenesis combined therapies for HCC.

Size-dependent influences of nanoplastics on microbial consortium differentially inhibiting 2, 4-dichlorophenol biodegradation.

Nanoplastics (NPs), as a type of newly emerging pollutant, are ubiquitous in various environmental systems, one of which is coexistence with organic pollutants in wastewater, potentially influencing the pollutants' biodegradation. A knowledge gap exists regarding the influence of microbial consortium and NPs interactions on biodegradation efficiency. In this work, a 2,4-dichlorophenol (DCP) biodegradation experiment with presence of polystyrene nanoplastics (PS-NPs) with particle sizes of 100 nm (PS100) or 20 nm (PS20) was conducted to verify that PS-NPs had noticeable inhibitory effect on DCP biodegradation in a size-dependent manner. PS100 at 10 mg/L and 100 mg/L both prolonged the microbial stagnation compared to the control without PS-NPs; PS20 exacerbated greater, with PS20 at 100 mg/L causing a noticeable 6-day lag before the start-up of rapid DCP reduction. The ROS level increased to 1.4-fold and 1.8-fold under PS100 and PS20 exposure, respectively, while the elevated LDH under PS20 exposure indicated the mechanical damage to cell membrane by smaller NPs. PS-NPs exposure also resulted in a decrease in microbial diversity and altered the niches of microbial species, e.g., they decreased the abundance of some functional bacteria such as Brevundimonas and Comamonas, while facilitated some minor members to obtain more proliferation. A microbial network with higher complexity and less competition was induced to mediate PS-NPs stress. Functional metabolism responded differentially to PS100 and PS20 exposure. Specifically, PS100 downregulated amino acid metabolism, while PS20 stimulated certain pathways in response to more severe oxidative stress. Our findings give insights into PS-NPs environmental effects concerning microflora and biological degradation.

Optimizing boiler combustion parameters based on evolution teaching-learning-based optimization algorithm for reducing NOx emission concentration.

How to reduce a boiler's NOx emission concentration is an urgent problem for thermal power plants. Therefore, in this paper, we combine an evolution teaching-learning-based optimization algorithm with extreme learning machine to optimize a boiler's combustion parameters for reducing NOx emission concentration. Evolution teaching-learning-based optimization algorithm (ETLBO) is a variant of conventional teaching-learning-based optimization algorithm, which uses a chaotic mapping function to initialize individuals' positions and employs the idea of genetic evolution into the learner phase. To verify the effectiveness of ETLBO, 20 IEEE congress on Evolutionary Computation benchmark test functions are applied to test its convergence speed and convergence accuracy. Experimental results reveal that ETLBO shows the best convergence accuracy on most functions compared to other state-of-the-art optimization algorithms. In addition, the ETLBO is used to reduce boilers' NOx emissions by optimizing combustion parameters, such as coal supply amount and the air valve. Result shows that ETLBO is well-suited to solve the boiler combustion optimization problem.

Anlotinib combined with transarterial chemoembolization for unresectable hepatocellular carcinoma associated with hepatitis B virus: a retrospective controlled study.

Purpose: To investigate the efficacy and safety of combined treatment of anlotinib and transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (uHCC) associated with hepatitis B virus (HBV) infection. Methods: We retrospectively collected the data of 96 uHCC patients associated with HBV infection who received either TACE only (TO group; n = 64) or anlotinib combined with TACE (TA group; n = 32) from January 2017 to January 2021. The primary endpoint was overall survival (OS). The secondary outcomes included progression-free survival (PFS), tumor response according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RECIST 1.1, and adverse events (AEs). Results: The median OS and median PFS were significantly longer in the TA group compared to the TO group (17.6 months vs. 9.4 months, p = 0.018; 6.7 months vs. 3.8 months, p = 0.003, respectively). In addition, the overall objective response rate (ORR) and disease control rate (DCR) numerically increased in the TA group (mRECIST, ORR 65.6% vs. 46.9%, p = 0.064, DCR 90.6% vs. 85.9%, p = 0.382; RECIST 1.1, ORR 46.9% vs. 15.6%, p = 0.001, DCR 90.6% vs. 85.9%, p = 0.382, respectively). It was worth noting that no treatment-related mortality occurred during the study. The most common AEs included elevated transaminases (56.3%), decreased appetite (46.9%), and abdominal pain (37.5%) in the TA group. Although the incidence rate of grade 3/4 AEs was higher in the TA group, all of them were controllable. Conclusions: The combination of anlotinib and TACE has shown promising results in improving outcomes for patients with HBV-related uHCC, as compared to TACE monotherapy. In addition, this combination therapy has demonstrated a controllable safety profile. However, further validation is urgently needed through randomized controlled trials with large sample sizes.

Comprehensive analysis of ZNF692 as a potential biomarker associated with immune infiltration in a pan cancer analysis and validation in hepatocellular carcinoma.

Currently, the roles of ZNF692 have been documented exclusively in lung, colon, and cervical cancers. However, its involvement in pan cancer remains unknown. In this study, we employed bioinformatics analysis and experimental validation to investigate the role of ZNF692 in pan cancer. Our findings revealed aberrant expression of ZNF692 across various types of cancer. High expression of ZNF692 was associated with poor overall survival (OS) in ACC, COAD, KIRC, LAML, and LIHC. ZNF692 exhibited promising diagnostic potential in certain tumor types. A significant correlation was observed between high ZNF692 expression and advanced stages of ACC, BLCA, KICH, KIRC, LIHC, and OV. The expression of ZNF692 exhibited a significant association with microsatellite instability (MSI) in eight types of cancer and tumor mutational burden (TMB) in ten types of cancer. A noteworthy correlation was observed between ZNF692 expression and immune infiltration as well as immune checkpoints. Amplification of ZNF692 emerged as the most frequent alteration in pan cancer. ZNF692 was implicated in various biological processes, cellular components, and molecular functions within the context of pan cancer. It is plausible that ZNF692 may contribute to chemotherapy and potentially be linked to chemoresistance. We constructed a competing endogenous RNA (ceRNA) network involving AC009403.11/miR-126-3p/ZNF692 in hepatocellular carcinoma (HCC). The expression of ZNF692 exhibited a notable upregulation in HCC cell lines. Aberrant expression of ZNF692 was observed across various types of cancer. ZNF692 holds potential as a valuable diagnostic, prognostic, and therapeutic target in the context of pan cancer.

Hypovirulence-associated mycovirus epidemics cause pathogenicity degeneration of Beauveria bassiana in the field.

BACKGROUND: The entomogenous fungus Beauveria bassiana is used as a biological insecticide worldwide, wild B. bassiana strains with high pathogenicity in the field play an important role in controlling insect pests via not only screening of highly virulent strains but also natural infection, but the pathogenicity degeneration of wild strains severely affected aforementioned effects. Previous studies have showed that multiple factors contributed to this phenomenon. It has been extensively proved that the mycovirus infection caused hypovirulence of phytopathogenic fungi, which has been used for plant disease biocontrol. However, it remains unknown whether the mycovirus epidemics is a key factor causing hypovirulence of B. bassiana naturally in the field. METHODS: Wild strains of B. bassiana were collected from different geographic locations in Jilin Province, China, to clarify the epidemic and diversity of the mycoviruses. A mycovirus Beauveria bassiana chrysovirus 2 (BbCV2) we have previously identified was employed to clarify its impact on the pathogenicity of host fungi B. bassiana against the larvae of insect pest Ostrinia furnacalis. The serological analysis was conducted by preparing polyclonal antibody against a BbCV2 coat protein, to determine whether it can dissociate outside the host fungal cells and subsequently infect new hosts. Transcriptome analysis was used to reveal the interactions between viruses and hosts. RESULTS: We surprisingly found that the mycovirus BbCV2 was prevalent in the field as a core virus in wild B. bassiana strains, without obvious genetic differentiation, this virus possessed efficient and stable horizontal and vertical transmission capabilities. The serological results showed that the virus could not only replicate within but also dissociate outside the host cells, and the purified virions could infect B. bassiana by co-incubation. The virus infection causes B. bassiana hypovirulence. Transcriptome analysis revealed decreased expression of genes related to insect epidermis penetration, hypha growth and toxin metabolism in B. bassiana caused by mycovirus infection. CONCLUSION: Beauveria bassiana infected by hypovirulence-associated mycovirus can spread the virus to new host strains after infecting insects, and cause the virus epidemics in the field. The findings confirmed that mycovirus infection may be an important factor affecting the pathogenicity degradation of B. bassiana in the field.

Decoding functional cell-cell communication events by multi-view graph learning on spatial transcriptomics.

Cell-cell communication events (CEs) are mediated by multiple ligand-receptor (LR) pairs. Usually only a particular subset of CEs directly works for a specific downstream response in a particular microenvironment. We name them as functional communication events (FCEs) of the target responses. Decoding FCE-target gene relations is: important for understanding the mechanisms of many biological processes, but has been intractable due to the mixing of multiple factors and the lack of direct observations. We developed a method HoloNet for decoding FCEs using spatial transcriptomic data by integrating LR pairs, cell-type spatial distribution and downstream gene expression into a deep learning model. We modeled CEs as a multi-view network, developed an attention-based graph learning method to train the model for generating target gene expression with the CE networks, and decoded the FCEs for specific downstream genes by interpreting trained models. We applied HoloNet on three Visium datasets of breast cancer and liver cancer. The results detangled the multiple factors of FCEs by revealing how LR signals and cell types affect specific biological processes, and specified FCE-induced effects in each single cell. We conducted simulation experiments and showed that HoloNet is more reliable on LR prioritization in comparison with existing methods. HoloNet is a powerful tool to illustrate cell-cell communication landscapes and reveal vital FCEs that shape cellular phenotypes. HoloNet is available as a Python package at https://github.com/lhc17/HoloNet.

The aggregated biofilm dominated by Delftia tsuruhatensis enhances the removal efficiency of 2,4-dichlorophenol in a bioelectrochemical system.

Bioelectrochemical system is a prospective strategy in organic-contaminated groundwater treatment, while few studies clearly distinguish the mechanisms of adsorption or biodegradation in this process, especially when dense biofilm is formed. This study employed a single chamber microbial electrolysis cell (MEC) with two three-dimensional electrodes for removing a typical organic contaminant, 2,4-dichlorophenol (DCP) from groundwater, which inoculated with anaerobic bacteria derived from sewage treatment plant. Compared with the single biodegradation system without electrodes, the three-dimensional electrodes with a high surface enabled an increase of alpha diversity of the microbial community (increased by 52.6% in Shannon index), and provided adaptive ecological niche for more bacteria. The application of weak voltage (0.6 V) furtherly optimized the microbial community structure, and promoted the aggregation of microorganisms with the formation of dense biofilm. Desorption experiment proved that the contaminants were removed from the groundwater mainly via adsorption by the biofilm rather than biodegradation, and compared with the reactor without electricity, the bioelectrochemical system increased the adsorption capacity from 50.0% to 74.5%. The aggregated bacteria on the surface of electrodes were mainly dominated by Delftia tsuruhatensis (85.0%), which could secrete extracellular polymers and has a high adsorption capacity (0.30 mg/g electrode material) for the contaminants. We found that a bioelectrochemical system with a three-dimensional electrode could stimulate the formation of dense biofilm and remove the organic contaminants as well as their possible more toxic degradation intermediates via adsorption. This study provides important guidance for applying bioelectrochemical system in groundwater or wastewater treatment.

Hepatic Arterial Infusion Chemotherapy Plus Lenvatinib and Tislelizumab with or Without Transhepatic Arterial Embolization for Unresectable Hepatocellular Carcinoma with Portal Vein Tumor Thrombus and High Tumor Burden: A Multicenter Retrospective Study.

Purpose: The current therapeutic strategies for high-risk, unresectable hepatocellular carcinoma (HCC) patients demonstrate suboptimal outcomes. This study aimed to assess the clinical efficacy of the combined approach of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and tislelizumab, either with or without transhepatic arterial embolization (TAE), in managing HCC patients with portal vein tumor thrombus (PVTT) and significant tumor load. Patients and Methods: In this multicenter retrospective study, we analyzed patients diagnosed with primary, unresectable HCC presenting with PVTT and substantial tumor load who had undergone treatment with HAIC, lenvatinib, and tislelizumab, with or without TAE (referred to as the THLP or HLP group), between January 2019 and February 2022 across four medical centers in China. The outcomes included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS). Results: The study cohort comprised 100 patients, 50 each in the THLP and HLP groups. The THLP group demonstrated a significantly superior ORR (72% vs 52%, P=0.039). However, both groups exhibited comparable DCR (88% vs 76%, P=0.118), as assessed by the modified response evaluation criteria in solid tumors. The median OS and PFS for the entire cohort were 12.5 months (95% CI, 10.9-14.8) and 5.0 months (95% CI, 4.2-5.4), respectively. The THLP group exhibited a significantly extended OS (median, 14.1 vs 11.3 months, P=0.041) and PFS (median, 5.6 vs 4.4 months, P=0.037) in comparison to the HLP group. The most frequently reported treatment-related adverse events included abdominal pain and nausea, both reported by 59% of patients. Conclusion: The combination of HAIC, lenvatinib, tislelizumab, and TAE was feasible in HCC patients with PVTT and high tumor burden, with tolerable safety.