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Cytokine-induced killer (CIK) cells are heterogeneous lymphocytes from human peripheral blood mononucleated cells (PBMCs) co-cultured with several cytokines. The main purpose of this study is to evaluate the functional characteristics and anticancer ability of CIK cells from hepatocarcinoma (HCC) patients. CIK cells were activated ex-vivo and expanded from PBMCs from HCC patients. The immunophenotype and the ex-vivo killing ability of CIK cells were evaluated. Human CIK cells were intravenously injected into NOD/SCID mice to evaluate the in vivo anticancer ability. More than 70% of CIK cells were CD3+CD8+, and 15%-30% were CD3+CD56+. These cells expressed an increased number of activated natural killer (NK) receptors, such as DNAM1 and NKG2D, and expressed low-immune checkpoint molecules, including PD-1, CTLA-4, and LAG-3. Among the chemokine receptors expressed by CIKs, CXCR3 and CD62L were elevated in CD8+ T cells, representing the trafficking ability to inflamed tumor sites. CIK cells possess the ex-vivo anticancer activity to different cell lines. To demonstrate in vivo antitumor ability, human CIK cells could significantly suppress the tumor of J7 bearing NOD/SCID mice. Furthermore, human immune cells could be detected in the peripheral blood and on the tumors after CIK injection. This study revealed that CIK cells from HCC patients possess cytotoxic properties, and express increased levels of effector NK receptors and chemokine molecules and lower levels of suppressive checkpoint receptors. CIK cells can suppress human HCC ex-vivo and in vivo. Future clinical trials of human CIK cell therapy for HCC are warranted.

Malaria has had a major effect on the human genome, with many protective polymorphisms—such as the sickle-cell trait—having been selected to high frequencies in malaria-endemic regions 1 , 2 . The blood group variant Dantu provides 74% protection against all forms of severe malaria in homozygous individuals 3 – 5 , a similar degree of protection to that afforded by the sickle-cell trait and considerably greater than that offered by the best malaria vaccine. Until now, however, the protective mechanism has been unknown. Here we demonstrate the effect of Dantu on the ability of the merozoite form of the malaria parasite Plasmodium falciparum to invade red blood cells (RBCs). We find that Dantu is associated with extensive changes to the repertoire of proteins found on the RBC surface, but, unexpectedly, inhibition of invasion does not correlate with specific RBC–parasite receptor–ligand interactions. By following invasion using video microscopy, we find a strong link between RBC tension and merozoite invasion, and identify a tension threshold above which invasion rarely occurs, even in non-Dantu RBCs. Dantu RBCs have higher average tension than non-Dantu RBCs, meaning that a greater proportion resist invasion. These findings provide both an explanation for the protective effect of Dantu, and fresh insight into why the efficiency of P. falciparum invasion might vary across the heterogenous populations of RBCs found both within and between individuals. The rare blood group Dantu is known to protect against severe malaria, and a mechanism is proposed here: Dantu red blood cells have a high membrane tension that prevents invasion by malaria parasites.

Background Lenvatinib and atezolizumab plus bevacizumab(A + B) have been used for unresectable hepatocellular carcinoma (HCC) as first‐line therapy. Real‐world studies comparison of efficacy and safety in these two regimens are limited, we therefore conduct this study to investigate these issues. Methods We retrospectively reviewed patients received lenvatinib (n = 46) and A + B (n = 46) as first‐line systemic therapy for unresectable HCC in a tertiary medical center. Objective response rate (ORR), progression free survival (PFS), and overall survival (OS) were evaluated according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Inverse probability weighting (IPW) was performed for baseline clinical features balance. Results A total of 92 patients with median age of 63.8 year‐old, 78.3% male, 85.9% viral hepatitis infected, 67.4% BCLC stage C were enrolled. The median treatment and follow‐up duration were 4.7 months and 9.4 months, respectively. There was no significant difference in ORR (26.1% vs. 41.3%, p = 0.1226), PFS (5.9 vs. 5.3 months, p = 0.4066), and OS (not reached vs. not reached, p = 0.7128) between the lenvatinib and A + B groups. After IPW, the results of survival and response rate were also compared. Subgroup analysis suggested that using lenvatinib was not inferior to A + B in regards of PFS, including those with elder, Child‐Pugh class B, beyond up‐to‐seven, or portal vein invasion VP4 patients. Among the lenvatinib treated patients, multivariate analysis showed patients elder than 65‐year‐old was an independent predictor associated with shorter PFS (adjust HR: 2.085[0.914–4.753], p = 0.0213). The incidence rates of adverse events were similar between two groups (76 vs. 63%, p = 0.1740). Both of two regimens had similarly few impact on liver function by comparison of baseline, third month, and sixth month albumin‐bilirubin index and Child‐Pugh score. Conclusions The efficacy and safety of lenvatinib are similar to A + B as a first‐line systemic therapy for unresectable HCC. This study provides real‐world experience of lenvatinib and A + B as firstline treatment for unresectable HCC. The data showed that compared survival, response rate, and adverse events between two regimens.

Abstract Background Atezolizumab plus bevacizumab (atezo-bev) has been recommended for advanced hepatocellular carcinoma (HCC). High-dose external beam radiotherapy (RT) is recognized for its excellent local tumor control. The efficacy and safety of concurrent atezo-bev with RT for highly advanced HCC has been minimally explored. Methods In this preliminary retrospective study, we assessed patients with highly advanced HCC, characterized by Vp4 portal vein thrombosis or tumors exceeding 50% of liver volume, who received concurrent atezo-bev and RT (group A). Group A included 13 patients who received proton radiation at a dose of 72.6 GyE in 22 fractions, and one patient who received photon radiation at a dose of 54 Gy in 18 fractions. This group was compared with 34 similar patients treated atezo-bev alone as a control (group B). The primary objectives were to evaluate the objective response rate (ORR), overall survival (OS), and safety. Results Baseline characteristics were similar between groups, except for a higher incidence of Vp4 portal vein thrombosis in group A (78.6% vs. 21.4%, P = .05). Group A achieved a higher ORR (50.0% vs. 11.8%, P < .01) and a longer OS (not reached vs. 5.5 months, P = .01) after a median follow-up of 5.2 months. Multivariate analysis indicated that concurrent RT independently favored longer OS (hazard ratio: 0.18; 95% CI, 0.05-0.63, P < .01). Group A did not increase any grade adverse events (78.6% vs. 58.8%, P = .19) or severe adverse events of grade ≥ 3 (14.3% vs. 14.7%, P = .97) compared to group B. Conclusions The concurrent high-dose external beam radiotherapy appears to safely enhance the effectiveness of atezolizumab plus bevacizumab for highly advanced patients with HCC. Further studies are warranted to confirm these findings. This preliminary retrospective study assessed patients with highly advanced hepatocellular carcinoma, exploring the efficacy and safety of concurrent atezolizumab plus bevacizumab with high-dose external beam radiotherapy for these patients.

This study proposes a practical integration of an existing deep learning model (YOLOv9-E) and social participation GIS using multi-source remote sensing data to identify asbestos-containing materials located on the side of a building affected by light occlusions. These objects are often undetectable by traditional vertical or oblique photogrammetry, yet their precise localization is essential for effective removal planning. By leveraging the mobility and responsiveness of citizen investigators, we conducted fine-grained surveys in community spaces that were often inaccessible using conventional methods. The YOLOv9-E model demonstrated robustness on mobile-captured images, enriched with geolocation and orientation metadata, which improved the association between detections and specific buildings. By comparing results from Google Street View and field-based social imagery, we highlight the complementary strengths of both sources. Rather than introducing new algorithms, this study focuses on an applied integration framework to improve detection coverage, spatial precision, and participatory monitoring for environmental risk management. The dataset comprised 20,889 images, with 98% being used for training and validation and 2% being used for independent testing. The YOLOv9-E model achieved an mAP50 of 0.81 and an F1-score of 0.85 on the test set.

Background: Hepatocellular carcinoma (HCC) remains a significant concern for patients with chronic hepatitis C (HCV), even after achieving a sustained virological response (SVR) with direct-acting antivirals (DAAs) or interferon (IFN)-based therapies. This study compared the risk of HCC in patients with HCV who achieved SVR through the DAA versus IFN regimens. Methods: A retrospective analysis was conducted on 4806 HCV patients, without coinfection nor prior HCC history, treated at the Chang Gung Memorial Hospital, Taiwan (DAA: 2825, IFN: 1981). Kaplan–Meier and Cox regression analyses with propensity score matching (PSM) were used to adjust for baseline differences. Results: DAA-treated patients exhibited a higher incidence of HCC than IFN-treated patients before and after PSM (after PSM: annual: 1% vs. 0.5%; 6-year: 6% vs. 3%, p = 0.01). Both DAA and IFN patients had a decreased HCC incidence during follow-up (>3 vs. <3 years from the end of treatment: DAA: 1.43% vs. 1.00% per year; IFN: 0.47% vs. 0.36% per year, both p < 0.05). HCC incidence was higher in the first three years post-SVR in DAA-treated ACLD patients and then decreased (3.26% vs. 1.39% per year, p < 0.01). In contrast, HCC incidence remained constant in the non-ACLD and IFN-treated groups. Multivariate Cox regression identified age ≥ 60, male sex, BMI, AFP ≥ 6 ng/mL, FIB-4, and ACLD status as independent risk factors for HCC, but antiviral regimens were not an independent factor for HCC. Conclusion: DAA treatment significantly affects HCC risk primarily within three years post-treatment, especially in younger HCV patients with ACLD. HCC incidence was reduced after three years in ACLD patients treated by DAA, but continued surveillance was still necessary. However, patients under 60 without advanced liver disease may require less intensive follow-up.

Background Direct-acting antiviral (DAA) therapy for chronic hepatitis C (CHC) achieves high sustained virologic response (SVR) rates; however, hepatocellular carcinoma (HCC) can still develop after viral eradication. Reliable biomarkers for predicting the post-SVR HCC risk are lacking. This study aimed to identify baseline serum extracellular vesicle microRNAs (EV-miRNAs) associated with HCC development following SVR. Materials and methods Eleven CHC patients who achieved SVR were retrospectively enrolled as a discovery cohort to identify candidate EV-miRNAs at SVR12 predictive of future HCC. An independent validation cohort of 89 CHC patients was also analyzed. HCC development was defined as the occurrence of HCC at ≥ 12 months after SVR. EV-miRNA profiles were assessed by small RNA sequencing and validated using a miRNA enzyme immunoassay (miREIA). Results In the discovery cohort, four EV-miRNAs (EV-miR-1-3p, EV-miR-148a-3p, EV-miR-223-3p, and EV-miR-4433b-5p) were significantly different between patients who later developed HCC and those who remained HCC-free at SVR12. In the 89-patient validation cohort, 51 (57.3%) developed HCC with a median disease-free survival (DFS) of 23.1 months, and 12 (13.5%) patients died during a median follow-up of 77 months. High baseline EV-miR-1-3p and EV-miR-148a-3p levels and low EV-miR-4433b-5p were associated with remaining HCC-free. Elevated EV-miR-1-3p and EV-miR-148a-3p levels were also correlated with longer DFS ( p  < 0.05). In multivariate analysis, EV-miR-1-3p was the only independent predictor of longer DFS (adjusted hazard ratio [HR] 0.459, p  = 0.014) and improved overall survival (OS) (adjusted HR 0.390, p  = 0.016) after SVR12. Among all biomarkers evaluated, baseline EV-miR-1-3p demonstrated the highest predictive accuracy for HCC occurrence (area under the curve [AUC] 0.843, vs. 0.769 for alpha-fetoprotein [AFP] and 0.755 for FIB-4; p  < 0.001) and for OS (AUC 0.876, vs. 0.480 for AFP and 0.655 for FIB-4; p  < 0.001). Furthermore, patients with high EV-miR-1-3p levels showed higher platelet counts and albumin, and a lower proportion with FIB-4 ≥ 3.25, suggesting that high EV-miR-1-3p reflects better preserved liver function and less advanced fibrosis. Conclusions Baseline serum EV-miR-1-3p serves as a protective biomarker for stratifying HCC risk and predicting survival in CHC patients after HCV eradication via DAA therapy.

Trichomes in Prunus persica (L.) Batsch are crucial specialized structures that play a protective role against both biotic and abiotic stresses. The fruits with and without trichomes are respectively named as peach and nectarine. At the genetic level, the formation of trichome in peach is controlled by a single gene, PpMYB25 , at the G locus. Peach ( GG or Gg ) is dominant to nectarine ( gg ), but such regulatory role was reported in a small-scale accession. In this study, we performed large-scale genotype and phenotype screening on 295 accessions. Almost all accessions supported the casual relationship between trichome formation and PpMYB25 . However, a peach to nectarine mutant, named Maravilha Nectarine Mutant (MN), was discovered to possess a putative functional PpMYB25 gene sequence ( Gg ) but revealed nectarine phenotype. Comparative transcriptomic analyses revealed that PpMYB25 transcript was absent in MN. Correlation analyses also demonstrated that the PpMYB25 -mediated regulatory network was abolished in MN. In summary, our results demonstrated an alternative mechanism beyond genetic regulation on trichome formation.

Lateral epicondylalgia (LE), a common overuse syndrome of the extensor muscle and tendons on the lateral epicondyle, causes persistent severe musculoskeletal pain on the outer part of the elbow. Fu’s subcutaneous needling (FSN), a newly invented subtype of acupuncture and dry needling, is a new trend and potential treatment of LE by targeting the myofascial trigger points (MTrPs). However, no scientific evidence is available to support this method. This study aims to evaluate the distal FSN treatment on the LE by measuring pain-related scales, such as visual analog scale (VAS), pressure pain threshold (PPT), muscle tissue hardness (TH), pain-free grip (PFG), and the functional outcome by a patient-rated tennis elbow evaluation (PRTEE) questionnaire study. A total of 60 LE patients were randomly divided into FSN (n = 30) and transcutaneous electrical nerve stimulation (TENS, n = 30) as the control group. Every subject was treated with three regimens and followed up for 15 days. Results showed that FSN has an immediate effect on VAS, PPT, TH, and PFG. Moreover, sustained effects on pain relief were followed up to 15 days. Pain remission was consistent with long-term PRTEE results. Overall, FSN is a safe and efficient therapy option for LE, significantly improving pain relief and activity difficulty with immediate, short-term, and long-term effectiveness. This trial is registered with ClinicalTrials.gov NCT03605563.