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Tiantian Xuan,1 Zhanmei Wang,1 Sibo Meng,1 Jiaxin Li,1 Jisheng Li,2 Fangli Cao,1,* Linli Qu1,* 1Department of Medical Oncology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China; 2Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fangli Cao; Linli Qu, Department of Medical Oncology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, Shandong, 266035, People’s Republic of China, Tel +86-18561811936 ; +86-18561811457, Email caofangliqilu@163.com; qulinli2021@163.comPurpose: Cetuximab (CET) combined with chemotherapy significantly improved the survival in RAS and RAF wild-type metastatic colorectal cancer (mCRC) patients, while clinical evidence was lacking on the use of maintenance therapy (MT). The study aimed to explore the role of maintenance therapy following Cetuximab + chemotherapy and the optimal Cetuximab-based maintenance therapy regimen.Patients and Methods: We retrospectively reviewed data on the efficacy and safety of CET-based MT in patients with mCRC who achieved disease control after induction therapy.Results: Eighty-one patients with mCRC who achieved disease control after CET + chemotherapy induction were enrolled. Overall median progression-free survival (PFS) was 10.5 (95% CI = 8.8– 12.2) months and median maintenance/observation PFS (mnPFS) was 6.0 (95% CI = 5.0– 7.0) months. Among these 81 patients, 61 patients were prescribed MT (CET alone for 21 patients and CET + chemotherapy for 40 patients). Median PFS and mnPFS in the MT group were significantly longer than those for the non-MT group. Different MT regimens did not affect PFS and mnPFS significantly. Univariate and multivariate analysis demonstrated MT, complete response/partial response during induction therapy, and absence of peritoneal metastasis to be positively associated with longer PFS and mnPFS. Treatment-related adverse events (AEs) were tolerable during MT, and AE-related deaths were not observed.Conclusion: MT with CET or CET + chemotherapy was an appropriate option following initial induction chemotherapy for patients with RAS and RAF wild-type mCRC. This strategy endowed survival benefits and a tolerable safety profile.Keywords: colorectal cancer, maintenance therapy, cetuximab, RAS and RAF wild-type, targeted therapy

Abstract Among the most prevalent neurodevelopmental disorders, Autism Spectrum Disorder (ASD) is highly diverse showing a broad phenotypic spectrum. ASD also couples with a broad range of mutations, both de novo and inherited. In this study, we used a proprietary SNP genotyping chip to analyze the genomic DNA of 250 Vietnamese children diagnosed with ASD. Our Single Nucleotide Polymorphism (SNP) genotyping chip directly targets more than 800 thousand SNPs in the genome. Our primary focus was to identify pathogenic/likely pathogenic mutations that are potentially linked to more severe symptoms of autism. We identified and validated 23 pathogenic/likely pathogenic mutations in this initial study. The data shows that these mutations were detected in several cases spanning multiple biological pathways. Among the confirmed SNPs, mutations were identified in genes previously known to be strongly associated with ASD such as SLCO1B1, ACADSB, TCF4, HCP5, MOCOS, SRD5A2, MCCC2, DCC, and PRKN while several other mutations are known to associate with autistic traits or other neurodevelopmental disorders. Some mutations were found in multiple patients and some patients carried multiple pathogenic/likely pathogenic mutations. These findings contribute to the identification of potential targets for therapeutic solutions in what is considered a genetically heterogeneous neurodevelopmental disorder.

Striped catfish is one of the most important farmed fish species in Vietnam but often susceptible to hemorrhagic septicemia caused by Aeromonas hydrophila. Phage therapy is a promising solution alternative to antibiotic usage due to the bacterial antibiotic resistance. In this study, five individual factors including molasses concentration, KH2PO4 concentration, yeast extract concentration, bacterial culture time and phage collection time were investigated for their effects on the producion of phage TG25P. Plackett-Burman design revealed that the bacterial culture time, phage collection time and molasses concentration were the most significant factors affecting the phage production. Application of response surface methodology for optimization of phage production showed that optimal values for these variables were 1.76 h, 2.22 h and 2.03 g/L, respectively. In the optimized medium, the phage production of (1.44 ( 0.2) ( 109 PFU/mL was obtained, which agreed well with the predicted value of 1.37 ( 109 PFU/mL. The findings really help us produce phage TG25P under the optimal condition at a low cost.

Abstract Breast cancer cells release a large quantity of biocargo‐bearing extracellular vesicles (EVs), which mediate intercellular communication within the tumour microenvironment and promote metastasis. To identify EV‐bound proteins related to metastasis, we used mass spectrometry to profile EVs from highly and poorly metastatic breast cancer lines of human and mouse origins. Comparative mass spectrometry indicated that integrins, including αv and β1 subunits, are preferentially enriched in EVs of highly metastatic origin over those of poorly metastatic origin. These results are consistent with our histopathological findings, which show that integrin αv is associated with disease progression in breast cancer patients. Integrin αv colocalizes with the multivesicular‐body marker CD63 at a higher frequency in the tumour and is enriched in circulating EVs of breast cancer patients at late stages when compared with circulating EVs from early‐stage patients. With a magnetic bead‐based flow cytometry assay, we confirmed that integrins αv and β1 are enriched in the CD63+ subsets of EVs from both human and mouse highly metastatic cells. By analysing the level of integrin αv on circulating EVs, this assay could predict the metastatic potential of a xenografted mouse model. To explore the export mechanism of integrins into EVs, we performed immunoprecipitation mass spectrometry and identified members of the galectin family as potential shuttlers of integrin αvβ1 into EVs. In particular, knockdown of galectin‐3, but not galectin‐1, causes a reduction in the levels of cell surface integrins β1 and αv, and decreases the colocalization of these integrins with CD63. Importantly, knockdown of galectin‐3 leads to a decrease of integrin αvβ1 export into the EVs concomitant with a decrease in the metastatic potential of breast cancer cells. Moreover, inhibition of the integrin αvβ1 complex leads to a reduction in the binding of EVs to fibronectin, suggesting that integrin αvβ1 is important for EV retention in the extracellular matrix. EVs retained in the extracellular matrix are taken up by fibroblasts, which differentiate into cancer associated fibroblasts. In summary, our data indicate an important link between EV‐bound integrin αvβ1 with breast cancer metastasis and provide additional insights into the export of integrin αvβ1 into EVs in the context of metastasis.

Summary: Background: Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminium hydroxide adjuvant. Methods: We conducted a dose-escalation, open label trial (phase 1) and a randomized, double-blind, placebo-controlled trial (phase 2) to evaluate the safety and immunogenicity of the Nanocovax vaccine (in 25 mcg, 50 mcg, and 75 mcg doses, aluminium hydroxide adjuvanted (0·5 mg/dose) in 2-dose regime, 28 days apart (ClinicalTrials.gov number, NCT04683484). In phase 1, 60 participants received two intramuscular injection of the vaccine following dose-escalation procedure. The primary outcomes were reactogenicity and laboratory tests to evaluate the vaccine safety. In phase 2, 560 healthy adults received either vaccine doses similar in phase 1 (25 or 50 or 75 mcg S antigen in 0·5 mg aluminium per dose) or adjuvant (0·5 mg aluminium) in a ratio of 2:2:2:1. One primary outcome was the vaccine safety, including solicited adverse events for 7 day and unsolicited adverse events for 28 days after each injection as well as serious adverse event or adverse events of special interest throughout the study period. Another primary outcome was anti-S IgG antibody response (Index unit/ml). Secondary outcomes were surrogate virus neutralisation (inhibition percentage), wild-type SARS-CoV-2 neutralisation (dilution fold), and T-cell responses by intracellular staining for interferon gamma (IFNg). Anti-S IgG and neutralising antibody levels were compared with convalescent serum samples from symptomatic Covid-19 patients. Findings: For phase 1 study, no serious adverse events were observed for all 60 participants. Most adverse events were grade 1 and disappeared shortly after injection. For phase 2 study, after randomisation, 480 participants were assigned to receive the vaccine with adjuvant, and 80 participants were assigned to receive the placebo (adjuvant only). Reactogenicity was absent or mild in the majority of participants and of short duration (mean ≤3 days). Unsolicited adverse events were mild in most participants. There were no serious adverse events related to Nanocovax. Regarding the immunogenicity, Nanocovax induced robust anti-S antibody responses. In general, there humoral responses were similar among vaccine groups which reached their peaks at day 42 and declined afterward. At day 42, IgG levels of vaccine groups were 60·48 [CI95%: 51·12–71·55], 49·11 [41·26–58·46], 57·18 [48·4-67·5] compared to 7·10 [6·32-13·92] of convalescent samples. IgG levels reported here can be converted to WHO international standard binding antibody unit (BAU/ml) by multiplying them to a conversion factor of 21·8. Neutralising antibody titre of vaccine groups at day 42 were 89·2 [52·2–152·3], 80·0 [50·8–125.9] and 95·1 [63·1–143·6], compared to 55·1 [33·4-91·0] of the convalescent group. Interpretation: Up to day 90, Nanocovax was found to be safe, well tolerated, and induced robust immune responses. Funding: This work was funded by the Coalition for Epidemic Preparedness Innovations (CEPI), the Ministry of Science and Technology of Vietnam, and Nanogen Pharmaceutical Biotechnology JSC.

Soybean Glicine max. (L.) Merr. is one of the most major food crops. In some areas, its responses to different climates have not been well studied, particularly in tropical countries where other crops are more dominant. Accordingly, we adopted the SIMPLE crop model to investigate the responses of soybeans to the climate. We conducted two experiments on crop growth in the Summer–Autumn season of 2020, and Winter–Spring 2021 in the Hoa Binh Commune, in the Mekong Delta, Vietnam, which is an area that is vulnerable to climate change impacts, to obtain data for our model input and assessment. The assessment was concerned with the effects of climate variables (temperature and CO2) on soybean biomass and yield. The results indicated that the SIMPLE model performed well in simulating soybean yields, with an RRMSE of 9–10% overall. The drought stress results showed a negative impact on the growth and development of soybeans, although drought stress due to less rainfall seemed more serious in Spring–Winter 2021 than in Summer–Autumn 2020. This study figured out the trend that higher temperatures can shorten biomass development and lead to yield reduction. In addition, soybeans grown under high CO2 concentrations of 600 ppm gave a higher biomass and a greater yield than in the case with 350 ppm. In conclusion, climate variance can affect the soybean yield, which can be well investigated using the SIMPLE model.

Neoantigen delivery using extracellular vesicles (EVs) has gained extensive interest in recent years. EVs derived from tumour cells or immune cells have been used to deliver tumour antigens or antitumor stimulation signals. However, potential DNA contamination from the host cell and the cost of large‐scale EV production hinder their therapeutic applications in clinical settings. Here, we develop an antigen delivery platform for cancer vaccines from red blood cell‐derived EVs (RBCEVs) targeting splenic DEC‐205+ dendritic cells (DCs) to boost the antitumor effect. By loading ovalbumin (OVA) protein onto RBCEVs and delivering the protein to DCs, we were able to stimulate and present antigenic OVA peptide onto major histocompatibility complex (MHC) class I, subsequently priming activated antigen‐reactive T cells. Importantly, targeted delivery of OVA using RBCEVs engineered with anti‐DEC‐205 antibody robustly enhanced antigen presentation of DCs and T cell activation. This platform is potentially useful for producing personalised cancer vaccines in clinical settings. [ABSTRACT FROM AUTHOR]

The present work represents the first effort to evaluate the effect of an in vitro simulated human digestion model on the α-amylase and α-glucosidase inhibitory activities of Callerya speciosa root extracts. Through bioguided fractionation, a series of fractions were obtained from hexane (CSH) and ethyl acetate (CSE) extracts. Initial screening identified active fractions (CSH2, CSH3, CSE2, CSE3, and CSE4) for further in vitro digestion evaluation. The results showed a decrease in antioxidant activity across all samples after digestion, while a simultaneous increase in α-amylase and α-glucosidase inhibitory activities was observed during the small intestinal phase. Notably, compared with the undigested fraction, CSE3 demonstrated a 1.7-fold increase in α-amylase inhibition (IC50 = 0.86 mg/mL). Moreover, the α-glucosidase inhibitory activities of CSH3, CSE3, and CSE4 were significantly greater after digestion, with IC50 values of 0.18, 0.05, and 0.02 mg/mL, respectively. Impressively, during the small intestinal phase, the α-glucosidase inhibitory activities of CSH3, CSE3, and CSE4 were substantially greater than those of acarbose by 13.2-, 47.6-, and 119.0-fold, respectively, and greater than those of palmitic acid by 1.7-, 6.0-, and 15.0-fold, respectively. GC-MS and LC-ESI-MS/MS analyses identified isoflavonoids, fatty acids, and triterpenoids as key bioactive compounds in these fractions. The present work provided foundational insights for the future exploration of C. speciosa root extracts for diabetes management. [ABSTRACT FROM AUTHOR]

Abstract Hanbury-Brown and Twiss (HBT) effect is the foundation for stellar intensity interferometry. However, it is a phase insensitive two-photon interference effect. Here we extend the HBT interferometer by mixing intensity-matched reference fields with the input fields before intensity correlation measurement. With the freely available coherent state serving as the reference field, we experimentally demonstrate the phase sensitive two-photon interference effect when the input fields are thermal fields in either continuous wave or non-stationary pulsed wave and measure the complete complex second-order coherence function of the input fields without bringing them together from separate locations. Moreover, we discuss how to improve the signal level by using the more realistic continuous wave broadband anti-bunched light fields as the reference field. Our investigations pave the way for developing new technology of remote sensing and interferometric imaging with applications in long baseline high-resolution astronomy.

Striped catfish is one of the most important farmed fish species in Vietnam but often susceptible to hemorrhagic septicemia caused by Aeromonas hydrophila. Phage therapy is a promising solution alternative to antibiotic usage due to the bacterial antibiotic resistance. In this study, five individual factors including molasses concentration, KH2PO4 concentration, yeast extract concentration, bacterial culture time and phage collection time were investigated for their effects on the producion of phage TG25P. Plackett-Burman design revealed that the bacterial culture time, phage collection time and molasses concentration were the most significant factors affecting the phage production. Application of response surface methodology for optimization of phage production showed that optimal values for these variables were 1.76 h, 2.22 h and 2.03 g/L, respectively. In the optimized medium, the phage production of (1.44 ± 0.2) x 109 PFU/mL was obtained, which agreed well with the predicted value of 1.37 x 109 PFU/mL. The findings really help us produce phage TG25P under the optimal condition at a low cost. [ABSTRACT FROM AUTHOR]

Abstract Due to systematic errors in models and the special geographic location of eastern China, most global climate models exhibit significant biases in predicting summer precipitation in this region. This study evaluates the North American Multi-Model Ensemble (NMME) forecasts for eastern China, with a lead time of six months.While NMME simulates precipitation climatology well, it poorly predicts anomalies. Using the Res34-Unet deep learning post-processing method, which has been proven to enhance NMME’s forecasts, we explore that Western Pacific Subtropical High (WPSH) and sea surface temperature (SST) are critical in enhancing forecast accuracy. Among the four models evaluated, only GEM-NEMO (correlation of 0.538 with the WPSH) and CanSIPS-IC3 (which partly captured the impact of SST anomalies on precipitation) partially reflected the key factors identified by deep learning. Simulating these factors more accurately could greatly enhance NMME’s predictive skill for summer precipitation.

Abstract Backgrounds Diagnostic prediction is a central application that spans various medical specialties and scenarios, sequential diagnosis prediction is the process of predicting future diagnoses based on patients' historical visits. Prior research has underexplored the impact of irregular intervals between patient visits on predictive models, despite its significance. Method We developed the Multi-task Fusion Visit Interval for Sequential Diagnosis Prediction (MISDP) framework to address this research gap. The MISDP framework integrated sequential diagnosis prediction with visit interval prediction within a multi-task learning paradigm. It uses positional encoding and interval encoding to handle irregular patient visit intervals. Furthermore, it incorporates historical attention residue to enhance the multi-head self-attention mechanism, focusing on extracting long-term dependencies from clinical historical visits. Results The MISDP model exhibited superior performance across real-world healthcare dataset, irrespective of the training data scarcity or abundance. With only 20% training data, MISDP achieved a 4. 2% improvement over KAME; when training data ranged from 60 to 80%, MISDP surpassed SETOR, the top baseline, by 0. 8% in accuracy, underscoring its robustness and efficacy in sequential diagnosis prediction task. Conclusions The MISDP model significantly improves the accuracy of Sequential Diagnosis Prediction. The result highlights the advantage of multi-task learning in synergistically enhancing the performance of individual sub-task. Notably, irregular visit interval factors and historical attention residue has been particularly instrumental in refining the precision of sequential diagnosis prediction, suggesting a promising avenue for advancing clinical decision-making through data-driven modeling approaches.

Recently, nanovaccine-based immunotherapy has been robustly investigated due to its potential in governing the immune response and generating long-term protective immunity. However, the presentation of a tumor peptide-major histocompatibility complex to T lymphocytes is still a challenge that needs to be addressed for eliciting potent antitumor immunity. Type 1 conventional dendritic cell (cDC1) subset is of particular interest due to its pivotal contribution in the cross-presentation of exogenous antigens to CD8+ T cells. Here, the DC-derived nanovaccine (denoted as Si9GM) selectively targets cDC1s with marginal loss of premature antigen release for effective stimulator of interferon genes (STING)-mediated antigen cross-presentation. Bone marrow dendritic cell (BMDC)-derived membranes, conjugated to cDC1-specific antibody (αCLEC9A) and binding to tumor peptide (OVA257-264), are coated onto dendrimer-like polyethylenimine (PEI)-grafted silica nanoparticles. Distinct molecular weight-cargos (αCLEC9A-OVA257-264 conjugates and 2′3′-cGAMP STING agonists) are loaded in hierarchical center-radial pores that enables lysosome escape for potent antigen-cross presentation and activates interferon type I, respectively. Impressively, Si9GM vaccination leads to the upregulation of cytotoxic T cells, a reduction in tumor regulatory T cells (Tregs), M1/M2 macrophage polarization, and immune response that synergizes with αPD-1 immune checkpoint blockade. This nanovaccine fulfills a dual role for both direct T cell activation as an artificial antigen-presenting cell and DC subset maturation, indicating its utility in clinical therapy and precision medicine.

The Diospyros genus (Ebenaceae) has significant economic value. During field surveys, we discovered a Diospyros specimen showing morphological overlap with both D. oleifera and D. kaki var. silvestris, provisionally named Diospyros aff. oleifera. To resolve its taxonomy, we sequenced and analyzed its chloroplast genome. The complete chloroplast genome is 157,732 bp with a quadripartite structure. mVISTA analysis revealed unique sequence variations compared to related species. Phylogenetic analysis using 75 protein-coding genes grouped it with D. oleifera, indicating their close relationship. Our findings suggest this specimen likely represents a novel, undescribed species. This study provides insights into Diospyros diversity and a foundation for future research.

Abstract Background Previous studies demonstrated thyroid stimulating hormone (TSH) plays an important role in regulating lipid metabolism, but the relationship between the two is controversial. Meanwhile, it has not been reported in a population with major depressive disorder (MDD). Methods We divided 1718 first-episode and drug naïve patients with MDD into a TSH abnormal group (TSH-AB) and a TSH normal group (TSH-NOR). The participants in the two groups were assessed by the Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA) and the positive subscale of Positive and Negative Syndrome Scale. The patients’ blood was tested for TSH, free T3, free T4, fasting blood glucose, lipid indexes and body mass index was recorded. Results The participants in the TSH-AB group had significantly higher HAMD scores, HAMA scores and total scores of positive symptoms, as well as higher incidence of suicide attempts than those in the TSH-NOR group, accompanied by significantly higher thyroglobulin antibodies, thyroid peroxidase antibodies, fasting blood glucose values, total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels compared with those of TSH-NOR patients. However, the high-density lipoprotein cholesterol (HDL-C) of TSH-AB patients was lower than those of TSH-NOR patients. TSH values were positively correlated with TC, TG, and LDL-C values, and negatively correlated with HDL-C value. Conclusion TSH was highly correlated with abnormal lipid metabolism in patients with MDD. The specific molecular mechanism of the relationship between TSH, lipid metabolism and the development of depression needs to be further in-depth investigation.

Kidney transplantation (KT) is a preferred treatment for end-stage renal disease (ESRD) because it offers better long-term survival and cost-effectiveness compared to dialysis. Significant global disparities persist in access to KT, particularly in low- and middle-income countries (LMICs). This study aims to assess the epidemiology and outcomes of KT in LMICs while examining the relationship between a country’s income level and its KT prevalence. A systematic review of the literature was conducted, with searches of PubMed, Scopus, and Web of Science from inception to 31 May 2024. Relevant articles reporting on the epidemiology and outcomes of KT or ESRD patients undergoing kidney replacement therapy (KRT) in LMICs were included. A total of 8054 articles were identified, with 972 articles selected for full-text screening after initial title and abstract review. Following full-text screening, 35 articles met the inclusion criteria. The data showed significant variation in KRT and KT prevalence across different geographical locations. Higher-income countries within LMICs tended to have higher KT prevalence rates. Barriers such as inadequate healthcare infrastructure, limited financial resources, and insufficient organ donation frameworks were identified as contributing factors to the low KT rates in these regions. The study highlights the disparities in KT access and prevalence in LMICs, underscoring the need for targeted interventions and international collaboration to address these gaps. Efforts to increase both living and deceased donor transplants, expand health system capacity, and incorporate KT in healthcare planning are needed to close this gap. Global partnerships spearheaded by organizations such as The Transplantation Society (TTS) and the International Society of Nephrology (ISN) are crucial for improving KT rates and outcomes in LMICs.

Begonia pedatifida has persistently been utilized as a traditional folk herbal medicine. This study has sequenced the chloroplast genome of B. pedatifida to establish its genomic characteristics and to discern its phylogenetic relationships with other closely related species. The chloroplast genome structure of B. pedatifida reveals a circular molecule with a length of 169,606 bp, including a large single copy (LSC) region of 76,086 bp, a small single copy (SSC) region of 18,314 bp, and a pair of inverted repeats (IRS) region of 37,603 bp. The entire genome contains 138 genes, which consist of 88 protein-coding genes, 42 tRNA genes, and 8 rRNA genes. Phylogenetic analysis suggests that B. pedatifida is closely related to Begonia emeiensis, Begonia jinyunensis, and Begonia pulchrifolia, sharing a common ancestor and forming sister lineages. This research provides genetic information for further study on B. pedatifida.

Solanum pseudocapsicum Linnaeus 1753, a popular indoor potted plant known for its ornamental fruits, had its chloroplast genome sequenced in this study to determine its phylogenetic relationship with other related species and to construct a phylogenetic analysis tree. The research findings are as follows: 1. The chloroplast genome of S. pseudocapsicum comprises a large single-copy (LSC) region of 86,260 base pairs, a small single-copy (SSC) region of 18,325 base pairs, and two inverted repeat (IR) regions, each measuring 25,390 base pairs in length. 2. The G + C content of the entire chloroplast genome is 37.59%, with the highest G + C content found in the IR regions, reaching 43.03%; followed by the LSC region, which has a G + C content of 35.68%; and the lowest in the SSC region, with a G + C content of 31.53%. 3. The genome contains 127 genes, including 82 protein-coding genes, 37 tRNA genes, and 8 rRNA genes, with 18 genes duplicated in the IR regions. 4. Phylogenetic analysis revealed that S. pseudocapsicum, Solanum betaceum, Solanum laciniatum, and Solanum nitidum are genetically closely related and are located on the same branch of the phylogenetic tree, indicating a close relationship among them. This study provides a foundation for the identification, classification, and exploration of genetic diversity within the Solanum genus.

Abstract Background Our research endeavored to develop a robust predictive signature grounded in super-enhancer-related genes (SERGs), with the dual objectives of forecasting survival outcomes and evaluating the tumor immune microenvironment (TiME) in hepatocellular carcinoma (HCC). Methods HCC RNA-sequencing data were retrieved from The Cancer Genome Atlas (TCGA), and 365 patients were randomly assigned to training or testing sets in 1:1 ratio. SERGs of HCC were downloaded from Super-Enhancer Database (SEdb). On the basis of training set, a SERGs signature was identified, and its prognostic value was confirmed by internal and external validation (GSE14520) sets. We subsequently examined the model for potential functional enrichment and the degree of tumor immune infiltration. Additionally, we carried out in vitro experiments to delve into the biological functions of CBX2 gene. Results An SE-related prognostic model including CBX2, TPX2, EFNA3, DNASE1L3 and SOCS2 was established and validated. According to this risk model, patients in the high-risk group had a significantly worse prognosis, and their immune cell infiltration was significantly different from that of low-risk group. Moreover, the high-risk group exhibited a significant enrichment of tumor-associated pathological pathways. The SERGs signature can generally be utilized to screen HCC patients who are likely to respond to immunotherapy, as there is a positive correlation between the risk score and the Tumor Immune Dysfunction and Exclusion (TIDE) score. Furthermore, the downregulation of the CBX2 gene expression was found to inhibit HCC cell viability, migration, and cell cycle progression, while simultaneously promoting apoptosis. Conclusions We developed a novel HCC prognostic model utilizing SERGs, indicating that patients with high-risk score not only face a poorer prognosis but also may exhibit a diminished therapeutic response to immune checkpoint inhibitors (ICIs). This model is designed to tailor personalized treatment strategies to the individual needs of each patient, thereby improving the overall clinical outcomes for HCC patients. Furthermore, CBX2 is a promising candidate for therapeutic intervention in HCC.

The article gives an in-depth understanding of the commitment to corporate social responsibility (CSR) on labour under the new generation of free trade agreements (FTAs) of the European Union (EU), and especially, the EU – Vietnam Free Trade Agreement (EVFTA). Following that, via the EU’s foreign and trade policies, this research clarifies the history as well as the evolution of the CSR commitments in the EU’s new generation FTAs. On that basis, this article also delves into the nature of CSR commitments related to labour in the EVFTA. Last but not least, the article reviews the current legislation of the EU and its member states as partners and suggests different policy implications that Vietnam and other developing nations might adopt to execute their CSR commitments in the context of global sustainable development.

Abstract Background Posterior reversible encephalopathy syndrome (PRES) is an uncommon neurological disorder which is characterised by variable symptoms. The transient clinical condition may be underestimated and misdiagnosed as other conditions, especially, among pregnant women with severe preeclampsia, eclampsia, and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome in the puerperium. We hereby contribute to the literature this rare complication and hightlight the appropriate management of PRES . Presentation case A pregnant woman (gravida 3, parity 2) had a normal antenatal course. However, she was diagnosed with severe preeclampsia and HELLP syndrome at 29 weeks and 5 days of gestation. Therefore, she was indicated for a medical termination of pregnancy following a patient’s consent at our tertiary referral hospital. Severely, the patient developed rapidly with altered mental health in early puerperium. In result, PRES was diagnosed based on a brain magnetic resonance imaging (MRI) evidence with typical findings. After a strict multidisciplinary management, the clinical condition improved after 5 days of onset and recovered completely after a 4-month follow-up without any sequelae. Conclusion In summary, despite its rarity, clinicians ought to be knowledgeable and raise an aware of PRES during pregnancy. Importantly, a brain imaging modalities should be taken into account among pregnant women with neurological symptoms subsequent to severe preeclampsia. In addition to early diagnosis, a timely appropriate treatment with multidisciplinary team is strongly indicated. Further studies with a large case series are required for this uncommon entity.

[Objective] This study aims to realize the simultaneous determination of fungicide residues in vegetables and fruits. [Methods] A liquid chromatography-tandem quadrupole composite linear ion TRAP-mass spectrometry (LC-QTRAP-MS/MS) method was established for the simultaneous determination of fungicide residues in fruits and vegetables. The samples were salted out with sodium acetate and anhydrous magnesium sulfate in an acetonitrile solution containing 0.1% acetic acid, magnesium sulfate, ethylenediamine-n-propyl silanized silica gel (PSA), octadecylsilane bonded silica gel (HC-C18) and multi-walled carbon nanotubes (MWCNTs) were used for purification. Mass spectrometry was conducted utilizing the enhanced ion scanning mode (MRM-IDA-EPI) and spectral library retrieval technology. The compounds were quantified using an external standard approach, comparing the retention time, ion pairs, and EPI spectral library retrieval. [Results] The 43 kinds of fungicides had a good linear relationship in the mass concentration range of 0.2~5.0 μg/L and 2.5~50.0 μg/L (R2>0.99). The limit of detection (LOD) was 0.1~5.0 μg/kg, and the limit of quantification (LOQ) was 0.4~10.0 μg/kg. The recoveries of the 43 kinds of fungicides were 65.1%～119.8% at three concentration levels, and the relative standard deviations were 0.8%～13.0%. [Conclusion] The established method is rapid, simple, and highly qualitative, and can be used for the screening, confirming and quantitative detection of 43 kinds of fungicides in fruits and vegetables.

Background: Exploring and identifying novel alleles of noncombined DNA Index System (CODIS) short tandem repeat (STR) loci in different ethnic groups is important for the establishment of forensic reference databases and study of population genetics. AIM: This study is aimed to explore the genetic polymorphism of 22 non-CODIS autosomal STR loci (D6S477, D18S535, D19S253, D15S659, D11S2368, D20S470, D1S1656, D22-GATA198B05, D8S1132, D4S2366, D21S1270, D13S325, D9S925, D3S3045, D14S608, D10S1435, D12S391, D7S3048, D17S1290, D5S2500, D2S1338, and D16S539) in Sierra Leone population and analyze the population genetic relationships in comparison with other populations. MATERIALS AND METHODS: The samples of a total of 495 unrelated individuals (274 females and 221 males) from Sierra Leone were examined by the Microreader™ 23SP ID System, and their genetic polymorphisms and associated forensic parameters were calculated. The genetic relationships between Sierra Leone population and other populations were evaluated as well. Results: A total of 287 alleles were observed with allelic frequencies ranging from 0.001 to 0.399. The cumulative power of discrimination (CPD) of the 22 autosomal STR loci was 0.999999999999999 99999999999999538. The cumulative probability of exclusion (CPE) of the 22 autosomal STR loci was 0.9999998514 (CPEdous) and 0.999999 9999826 (CPEtrios). All of the STR loci reached the Hardy–Weinberg equilibrium after Bonferroni correction. The population genetics analysis results demonstrated that Sierra Leone population exhibited distinctive genetic characteristics compared to those of East Asian populations and it had relatively close genetic distances to the Uygur population. Conclusion: The results of this study could enrich the forensic databases with Sierra Leone population. The 22 STR loci are highly polymorphic and could be used for forensic practice and population genetics studies.