Salvage haploidentical transplantation for graft failure after first haploidentical allogeneic stem cell transplantation: an updated experience.

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. However, there are no recommended regimens for second transplantations for graft failure, especially in the haploidentical transplant setting. We recently reported encouraging outcomes using a novel method (haploidentical transplantation from a different donor after conditioning with fludarabine and cyclophosphamide). Herein, we report updated outcomes in 30 patients using this method. The median time of the second transplantation was 96.5 (33-215) days after the first transplantation. Except for one patient who died at +19d and before engraftment, neutrophil engraftments were achieved in all patients at 11 (8-24) days, while platelet engraftments were achieved in 22 (75.8%) patients at 17.5 (9-140) days. The 1-year OS and DFS were 60% and 53.3%, and CIR and TRM was 6.7% and 33.3%, respectively. Compared with the historical group, neutrophil engraftment (100% versus 58.5%, p < 0.001) and platelet engraftment (75.8% versus 32.3%, p < 0.001) were better in the novel regimen group, and OS was also improved (60.0% versus 26.4%, p = 0.011). In conclusion, salvage haploidentical transplantation from a different donor using the novel regimen represents a promising option to rescue patients with graft failure after the first haploidentical transplantation.

Predicting the effect of chemicals on fruit using graph neural networks.

The neural network method is a type of machine learning that has made significant advances over the past few years in a variety of fields, particularly text, speech, images, videos, etc. In areas where data is unstructured, traditional machine learning has not been able to surpass the 'glass ceiling'; therefore, researchers have turned to neural networks as auxiliary tools to achieve significant breakthroughs or develop new research methods. An array of computational chemistry challenges can be addressed using neural networks, including virtual screening, quantitative structure-activity relationships, protein structure prediction, materials design, quantum chemistry, and property prediction, among others. This paper proposes a strategy for predicting the chemical properties of fruits by using graph neural networks, and it aims to provide some guidance to researchers and streamline the identification process.

Discovery of novel Thymol-TPP antibiotics that eradicate MRSA persisters.

The high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) strains and the formation of non-growing, dormant "persisters" subsets help bacteria evade antibiotic treatment and enhance bacterial resistance, which poses a serious threat to human life and health. It is urgent to discover novel antibacterial therapies effective against MRSA persisters. Thymol is a common nutraceutical with weak antibacterial and antitumor activities. A series of Thymol triphenylphosphine (TPP) conjugates (TPP-Thy3) was designed and synthesized. These compounds showed significantly improved inhibitory activity against Gram-positive bacteria compared with Thymol. Among them, Thy3d displayed a low probability of resistance selection and showed excellent biocompatibility. Interestingly, Thy3d elicited a rapid killing effect of MRSA persisters (99.999%) at high concentration. Fluorescence experiments, electron microscopy, molecular dynamics simulation and bilayer experiment confirmed that Thy3d conjugates exerted potent antimicrobial activity by disrupting the integrity of the membrane of bacterial even the persister. Furthermore, Thy3d exhibited considerable efficacy in a mouse model of subcutaneous murine MRSA infection. In summary, TPP-Thy3 conjugates are a series of novel antibacterial agents and could serve as a new therapeutic strategy for combating antibiotic resistance.

Multi-User Computation Offloading and Resource Allocation Algorithm in a Vehicular Edge Network.

In Vehicular Edge Computing Network (VECN) scenarios, the mobility of vehicles causes the uncertainty of channel state information, which makes it difficult to guarantee the Quality of Service (QoS) in the process of computation offloading and the resource allocation of a Vehicular Edge Computing Server (VECS). A multi-user computation offloading and resource allocation optimization model and a computation offloading and resource allocation algorithm based on the Deep Deterministic Policy Gradient (DDPG) are proposed to address this problem. Firstly, the problem is modeled as a Mixed Integer Nonlinear Programming (MINLP) problem according to the optimization objective of minimizing the total system delay. Then, in response to the large state space and the coexistence of discrete and continuous variables in the action space, a reinforcement learning algorithm based on DDPG is proposed. Finally, the proposed method is used to solve the problem and compared with the other three benchmark schemes. Compared with the baseline algorithms, the proposed scheme can effectively select the task offloading mode and reasonably allocate VECS computing resources, ensure the QoS of task execution, and have a certain stability and scalability. Simulation results show that the total completion time of the proposed scheme can be reduced by 24-29% compared with the existing state-of-the-art techniques.

Age and sex estimation in cephalometric radiographs based on multitask convolutional neural networks.

OBJECTIVES: Age and sex characteristics are evident in cephalometric radiographs (CRs), yet their accurate estimation remains challenging due to the complexity of these images. This study aimed to harness deep learning to automate age and sex estimation from CRs, potentially simplifying their interpretation. STUDY DESIGN: We compared the performance of 4 deep learning models (SVM, R-net, VGG16-SingleTask, and our proposed VGG16-MultiTask) in estimating age and sex from the testing dataset, utilizing a VGG16-based multitask deep learning model on 4,557 CRs. Gradient-weighted class activation mapping (Grad-CAM) was incorporated to identify sex. Performance was assessed using mean absolute error (MAE), specificity, sensitivity, F1 score, and the area under the curve (AUC) in receiver operating characteristic analysis. RESULTS: The VGG16-MultiTask model outperformed the others, with the lowest MAE (0.864±1.602) and highest sensitivity (0.85), specificity (0.88), F1 score (0.863), and AUC (0.93), demonstrating superior efficacy and robust performance. CONCLUSIONS: The VGG multitask model demonstrates significant potential in enhancing age and sex estimation from cephalometric analysis, underscoring the role of AI in improving biomedical interpretations.

[Characteristics of Epiphytic Bacterial Community on Submerged Macrophytes in Water Environment Supplemented with Reclaimed Water].

Biofilms attached to submerged macrophytes play an important role in improving the water quality of the water environment supplemented with reclaimed water. In order to explore the effects of reclaimed water quality and submerged macrophyte species on the characteristics of an epiphytic bacterial community, different types of submerged macrophytes were selected as research objects in this study. 16S rRNA high-throughput sequencing technology was used on the epiphytic bacteria and the surrounding environmental samples to analyze the bacterial community structure and functional genes. The results showed that approximately 20%-35% of the nitrogen and phosphorus nutrients were absorbed and utilized in the water environment supplemented with reclaimed water. However, the COD, turbidity, and chroma of the downstream water were significantly increased. The bacterial community of the biofilms attached to submerged macrophytes was significantly different from that in the surrounding environment (soil, sediment, and water body) and in the activated sludge that was treated by reclaimed water. In terms of bacterial community diversity, the richness and diversity were significantly lower than those of soil and sediment but higher than those of plankton bacteria in water. In terms of bacterial community composition, dominant genera and corresponding abundances were also different from those of other samples. The main dominant bacterial genera were Sphingomonas, Aeromonas, Pseudomonas, and Acinetobacter, accounting for 7%-40%, respectively. Both macrophyte species and the quality of reclaimed water (BOD5, TN, NH4+-N, and TP) could affect the bacterial community. However, the effect of water quality of the bacterial community was greater than that of macrophytes species. Additionally, the quality of reclaimed water also affected the abundance of functional genes in the bacterial community, and the relative abundance of nitrogen and phosphorus cycling functional genes was higher in areas with higher nitrogen and phosphorus concentrations.

Removal of Horizontally Impacted Mandibular Third Molars Using the Three-Piece or T-Shaped Tooth Sectioning Method.

BACKGROUND: The extraction of horizontally impacted mandibular third molars (HM3) can be a complicated surgery. Appropriate tooth sectioning methods can reduce the operation time and postoperative complications. PURPOSE: The current study compares operative time and postoperative pain between HM3 removed using the three-piece or T-shaped tooth sectioning techniques. STUDY DESIGN, SETTING, SAMPLE: A randomized single-blind prospective clinical trial on HM3 extraction was carried out between June and December 2022 in the Department of Oral and Maxillofacial Surgery, the Affiliated Stomatological Hospital, Southwest Medical University. Patients with local or systemic infection, poor oral hygiene, and systemic disease were excluded. PREDICTOR VARIABLE: The predictor variable was the tooth sectioning method. The subjects were randomized to a three-piece or T-shaped group. MAIN OUTCOME VARIABLE(S): The primary outcome variables were the operative time and postoperative pain measured using a visual analog scale (VAS). The secondary outcome variables were the rates of primary bleeding, mouth opening reduction, swelling, patient satisfaction measured using a VAS, and quality of life measured using a postoperative symptom severity scale. COVARIATES: The covariates included age, sex, side and classification of HM3, and the relationship of HM3 to the inferior alveolar nerve canal. ANALYSES: The data were analyzed using the independent samples t-test, paired t-test, χ2, and rank sum test. A significance level set at P < .05. RESULTS: The sample included 60 patients in the three-piece group and 66 patients in the T-shaped group. The operative time of the three-piece group (14.73 ± 3.21 minutes) was shorter than that of the T-shaped group (19.25 ± 4.29 minutes) (P < .05). On days 3 and 7, VAS of pain were 2.24 ± 1.89 and 0.15 ± 0.40 in the three-piece group and 3.95 ± 2.44 and 0.48 ± 0.68 in the T-shaped group (P < .05). The VAS of patient satisfaction in the three-piece group (6.05 ± 1.29) was better than the T-shaped group (4.90 ± 1.05) on day 7 (P < .05). CONCLUSION AND RELEVANCE: The three-piece tooth sectioning for HM3 removal was associated with shorter duration, slighter postoperative symptoms, and higher patient satisfaction and may be considered as a recommended practice for dentists.

Intra-individual comparison of Sonazoid contrast-enhanced ultrasound and SonoVue contrast-enhanced ultrasound in diagnosing hepatocellular carcinoma.

PURPOSE: To assess whether the diagnostic performance of Sonazoid contrast-enhanced ultrasound (SZUS) is non-inferior to that of SonoVue contrast-enhanced ultrasound (SVUS) in diagnosing hepatocellular carcinoma (HCC) in individuals with high risk. MATERIALS AND METHODS: This prospective study was conducted from October 2020 to May 2022 and included participants with a high risk of HCC who underwent SZUS and SVUS. All lesions were confirmed by clinical or pathological diagnosis. Each nodule was classified according to the Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System version 2017 (CEUS LI-RADS v2017) for SVUS and SZUS and the modified CEUS LI-RADS (using Kupffer phase defect instead of late and mild washout) for SZUS. The diagnostic performance of both two modalities for all observations was compared. Analysis of the vascular phase and Kupffer phase imaging characteristics of CEUS was performed. RESULTS: One hundred and fifteen focal liver lesions from 113 patients (94 HCCs, 12 non-HCC malignancies, and 9 benign lesions) were analysed. According to CEUS LI-RADS (v2017), SVUS and SZUS showed similar sensitivity (71.3% vs. 72.3%) and specificity (85.7% vs. 81.0%) in HCC diagnosis. However, the modified CEUS LI-RADS did not significantly improve the diagnostic efficacy of Sonazoid compared to CEUS LI-RADS v2017, having equivalent sensitivity (73.4% vs. 72.3%) and specificity (81.0% vs. 81.0%). The agreement between SVUS and SZUS for all observations was 0.610 (95% CI 0.475, 0.745), while for HCCs it was 0.452 (95% CI 0.257, 0.647). CONCLUSION: Using LI-RADS v2017, SZUS and SVUS showed non-inferior efficacy in evaluating HCC lesions. In addition, adding Kupffer phase defects to SZUS does not notably improve its diagnostic efficacy.

Synthesis of cis-(8b,14a)-hexahydro-14H-dibenzo[f,h]oxazolo[3,2-b]isoquinolin-14-ones via photo cascade reaction.

A concise method for the synthesis of cis-(8b,14a)-hexahydro-14H-dibenzo[f,h]oxazolo[3,2-b]isoquinolin-14-ones 2 via photo-induced 3-([1,1'-biphenyl]-2-yl)-1-(2-hydroxyethyl)pyridin-2(1H)-ones 1 was developed. Irradiation of 1 in the solution of toluene with a 313 nm UV light in the presence of HCl gave cis-(8b,14a)-9a-α-hexahydro-14H-dibenzo[f,h]oxazolo[3,2-b]isoquinoli n-14-ones and cis-(8b,14a)-9a-ß-hexahydro-14H-dibenzo[f,h]oxazolo[3,2-b]isoquinolin-14-ones 2 (2-α and 2-ß) in good yields. The protocol simultaneously constructs dearomatized phenanthrene ring and oxindolizidinones ring by photo cascade reaction to achieve high bonding efficiency and high atomic efficiency. Additionally, the antitumor activities of 2 was evaluated and compounds 2b-α, 2b-ß, 2j-ß and 2 k-α showed similar or better activity compared to the cisplatin against tumor cell lines of Leukemia HL-60, lung cancer A594, liver cancer SMMC-7721 and breast cancer MDA-MB-231.

First Report of Powdery Mildew on Berchemia floribunda Caused by Erysiphe berchemiae in China.

The genus Berchemia (family Rhamnaceae), a group of climbing plants, is mainly distributed in Asia, Africa, and South America. Berchemia plants are widely used in traditional medicine in some Asian countries (Inoshiri et al. 1987). For example, in Japan, B. racemosa (synonym B. floribunda) is used for the treatment of gallstones, liver diseases, neuralgia, and stomach cramps, and in China, B. floribunda is used for the treatment of rheumatism and lumbago. In August 2022, typical powdery mildew symptoms were observed on wild B. floribunda plants in Huaxi District, Guiyang, Guizhou Province, China. The incidence was approximately 60% among 100 B. floribunda plants observed outdoors. White colonies almost entirely covered on both adaxial and abaxial surfaces of all leaves on symptomatic plants. Infected leaves appeared curled or chlorotic, infection occasionally leading to defoliation. To describe the pathogen morphologically, fungal samples were collected from two individual B. floribunda plants and microscopically characterized. In these samples, hyphae were flexuous to straight, branched, septate, 3-6 µm wide, with lobed hyphal appressoria. Conidiophores were erect, flexuous to straight, and 50-160 µm long (n = 30). Foot cells were subcylindrical to slightly curved-sinuous at the base, 20-40 µm long (n = 30), followed by 2-3 shorter cells. Conidia formed singly, occasionally 2-3 in a chain. Conidia were ellipsoid to ovoid, 20-42 × 12-18 µm (n = 50), without fibrosin bodies. Chasmothecia were not found. For molecular identification, the ribosomal DNA internal transcribed spacers (ITSs) of the two fungal samples were amplified and sequenced using the ITS1/ITS4 primer pair (White et al. 1990). The obtained 649-bp ITS sequences (GenBank accession nos. OR414364 and OR414365, respectively) shared 100% identity, and they showed 99.52% identity with the ITS sequence (GenBank accession no. LC009934) of Erysiphe berchemiae. Phylogenetic analysis grouped OR414364 and OR414365 in a clade with LC009934. Based on morphological and molecular characteristics, the powdery mildew fungus from B. floribunda was identified as E. berchemiae (Braun and Cook 2012). The voucher specimen (accession no. GZNU-BFEE/0820/2022) were deposited at the School of Life Sciences, Guizhou Normal University. Pathogenicity was assessed by gently pressing naturally diseased leaves of B. floribunda onto leaves of three healthy potted 1-year-old B. floribunda plants. Three non-inoculated healthy plants were used as controls. The plants were incubated in a greenhouse at 25 ± 2°C, 80% relative humidity. Similar powdery mildew symptoms were observed on the inoculated plants 9 days after inoculation, whereas the control plants remained symptomless. The reisolated fungus from inoculated leaves was morphologically identical to that observed on the original diseased leaves, and the ITS sequence of the reisolated fungus shared 100% identity with OR414364 and OR414365, fulfilling Koch's postulates. E. berchemiae has previously been described as a powdery mildew pathogen on B. yunnanensis (Chen et al. 1987) and B. kulingensis (Chen 1993) in China and B. racemosa (synonym B. floribunda) in Japan (Braun and Cook 2012; Takamatsu et al. 2015), but this is the first report of E. berchemiae causing disease of B. floribunda in China. This work suggests that E. berchemiae is an important pathogen of Berchemia plants, at least for some species in the genus Berchemia.

Associations of muscle mass and strength with new-onset diabetes among middle-aged and older adults: evidence from the China health and retirement longitudinal study (CHARLS).

BACKGROUND: The associations of muscle mass and strength with new-onset Type 2 diabetes mellitus (T2DM) remain controversial. We aimed to longitudinally evaluate muscle mass and strength in predicting T2DM among Chinese middle-aged and older adults. METHODS: We enrolled 6033 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study (CHARLS), a cohort survey, between 2011 and 2012. The appendicular skeletal muscle mass (normalized by weight, ASM/BW%), relative hand grip strength (normalized by weight, HGS/BW), and five-repetition chair stand test (5CST). were all categorized into tertiles (lowest, middle, and highest groups) at baseline, respectively. Individuals were followed up until the occurrence of diabetes or the end of CHARLS 2018, whichever happened first. Cox proportional hazards models to calculate hazard ratios with 95% confidence intervals (CI) and mediation analysis were used. RESULTS: During follow-up, 815 (13.5%) participants developed T2DM. After adjusting for covariates, lower ASW/BW% was not associated with a higher risk of diabetes. Compared with individuals in the highest tertile of HGS/BW, those in the lowest tertile had 1.296 (95%CI 1.073-1.567) higher risk of diabetes. Compared with individuals in the lowest tertile of 5CST, those in the highest tertile had 1.329 times (95%CI 1.106-1.596) higher risk of diabetes. By subgroup, both the lowest HGS/BW and highest 5CST were risk factors for diabetes among obesity. The mediation analysis revealed that the effect of HGS/BW on the risk of diabetes is mainly mediated by insulin resistance. CONCLUSIONS: Lower muscle strength is associated with an increased risk of diabetes, especially in obese populations.

Paternal preconception alcohol consumption increased Angiotensin II-mediated vasoconstriction in male offspring cerebral arteries via oxidative stress-AT1R pathway.

Alcohol consumption is popular worldwidely and closely associated with cardiovascular diseases. Influences of paternal preconception alcohol consumption on offspring cerebral arteries are largely unknown. Male rats were randomly given alcohol or water before being mated with alcohol-naive females to produce alcohol- and control-sired offspring. Middle cerebral artery (MCA) was tested with a Danish Myo Technology wire myograph, patch-clamp, IONOPTIX, immunofluorescence and quantitative PCR. Alcohol consumption enhanced angiotensin II (AngII)-mediated constriction in male offspring MCA mainly via AT1R. PD123,319 only augmented AngII-induced constriction in control offspring. AngII and Bay K8644 induced stronger intracellular calcium transient in vascular smooth muscle cells (VSMCs) from MCA of alcohol offspring. L-type voltage-dependent calcium channel (L-Ca2+ ) current at baseline and after AngII-stimulation was higher in VSMCs. Influence of large-conductance calcium-activated potassium channel (BKC a ) was lower. Caffeine induced stronger constriction and intracellular calcium release in alcohol offspring. Superoxide anion was higher in alcohol MCA than control. Tempol and thenoyltrifluoroacetone alleviated AngII-mediated contractions, while inhibition was significantly higher in alcohol group. The mitochondria were swollen in alcohol MCA. Despite lower Kcnma1 and Prkce expression, many genes expressions were higher in alcohol group. Hypoxia induced reactive oxygen species production and increased AT1R expression in control MCA and rat aorta smooth muscle cell line. In conclusion, this study firstly demonstrated paternal preconception alcohol potentiated AngII-mediated vasoconstriction in offspring MCA via ROS-AT1R. Alcohol consumption increased intracellular calcium via L-Ca2+ channel and endoplasmic reticulum and decreased BKCa function. The present study provided new information for male reproductive health and developmental origin of cerebrovascular diseases.

Corrigendum: ATP6V0C is associated with febrile seizures and epilepsy with febrile seizures plus.

[This corrects the article DOI: 10.3389/fnmol.2022.889534.].

Omentin-1 inhibits the development of benign prostatic hyperplasia by attenuating local inflammation.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a prevalent disease affecting elderly men, with chronic inflammation being a critical factor in its development. Omentin-1, also known as intelectin-1 (ITLN-1), is an anti-inflammatory protein primarily found in the epithelial cells of the small intestine. This study aimed to investigate the potential of ITLN-1 in mitigating BPH by modulating local inflammation in the prostate gland. METHODS: Our investigation involved two in vivo experimental models. Firstly, ITLN-1 knockout mice (Itln-1-/-) were used to study the absence of ITLN-1 in BPH development. Secondly, a testosterone propionate (TP)-induced BPH mouse model was treated with an ITLN-1 overexpressing adenovirus. We assessed BPH severity using prostate weight index and histological analysis, including H&E staining, immunohistochemistry, and enzyme-linked immunosorbent assay. In vitro, the impact of ITLN-1 on BPH-1 cell proliferation and inflammatory response was evaluated using cell proliferation assays and enzyme-linked immunosorbent assay. RESULTS: In vivo, Itln-1-/- mice exhibited elevated prostate weight index, enlarged lumen area, and higher TNF-α levels compared to wild-type littermates. In contrast, ITLN-1 overexpression in TP-induced BPH mice resulted in reduced prostate weight index, lumen area, and TNF-α levels. In vitro studies indicated that ITLN-1 suppressed the proliferation of prostate epithelial cells and reduced TNF-α production in macrophages, suggesting a mechanism involving the inhibition of macrophage-mediated inflammation. CONCLUSION: The study demonstrates that ITLN-1 plays a significant role in inhibiting the development of BPH by reducing local inflammation in the prostate gland. These findings highlight the potential of ITLN-1 as a therapeutic target in the management of BPH.

Development and validation of a multi-modal ultrasomics model to predict response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

OBJECTIVES: To assess the performance of multi-modal ultrasomics model to predict efficacy to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) and compare with the clinical model. MATERIALS AND METHODS: This study retrospectively included 106 patients with LARC who underwent total mesorectal excision after nCRT between April 2018 and April 2023 at our hospital, randomly divided into a training set of 74 and a validation set of 32 in a 7: 3 ratios. Ultrasomics features were extracted from the tumors' region of interest of B-mode ultrasound (BUS) and contrast-enhanced ultrasound (CEUS) images based on PyRadiomics. Mann-Whitney U test, spearman, and least absolute shrinkage and selection operator algorithms were utilized to reduce features dimension. Five models were built with ultrasomics and clinical analysis using multilayer perceptron neural network classifier based on python. Including BUS, CEUS, Combined_1, Combined_2 and Clinical models. The diagnostic performance of models was assessed with the area under the curve (AUC) of the receiver operating characteristic. The DeLong testing algorithm was utilized to compare the models' overall performance. RESULTS: The AUC (95% confidence interval [CI]) of the five models in the validation cohort were as follows: BUS 0.675 (95%CI: 0.481-0.868), CEUS 0.821 (95%CI: 0.660-0.983), Combined_1 0.829 (95%CI: 0.673-0.985), Combined_2 0.893 (95%CI: 0.780-1.000), and Clinical 0.690 (95%CI: 0.509-0.872). The Combined_2 model was the best in the overall prediction performance, showed significantly better compared to the Clinical model after DeLong testing (P < 0.01). Both univariate and multivariate logistic regression analyses showed that age (P < 0.01) and clinical stage (P < 0.01) could be an independent predictor of efficacy after nCRT in patients with LARC. CONCLUSION: The ultrasomics model had better diagnostic performance to predict efficacy to nCRT in patients with LARC than the Clinical model.

Enhanced Fe(ii)/Fe(iii) cycle by boron enabled efficient Cr(vi) removal with microscale zero-valent iron.

Recently, researchers have been paying much attention to zero-valent iron (ZVI) in the field of pollution remediation. However, the depressed electron transport from the iron reservoir to the iron oxide shell limited the wide application of ZVI. This study was aimed at promoting the performance of microscale ZVI (mZVI) for hexavalent chromium (Cr(vi)) removal by accelerating iron cycle with the addition of boron powder. It was found that the addition of boron powder enhanced the Cr(vi) removal rate by 2.1 times, and the proportion of Cr(iii) generation after Cr(vi) removal process also increased, suggesting that boron could promote the reduction pathway of Cr(vi) to Cr(iii). By further comparing the Cr(vi) removal percentage of Fe(iii) with or without the boron powder, we found that boron powder could promote the percentage removal of Cr(vi) with Fe(iii) from 10.1% to 33.6%. Moreover, the presence of boron powder could decrease the potential gap values (ΔEp) between Fe(iii) reduction and Fe(ii) oxidation from 0.668 V to 0.556 V, further indicating that the added boron powder could act as an electron sacrificial agent to promote the reduction process of Fe(iii) to Fe(ii), and thus enhancing the reduction of Cr(vi) with Fe(ii). This study shed light on the promoted mechanism of Cr(vi) removal with boron powder and provided an environmentally friendly and efficient approach to enhance the reactivity of the mZVI powder, which would benefit the wide application of mZVI technology in the environmental remediation field.

Intrathecal morphine delivery at prepontine cistern to control refractory cancer-related pain: a case report of extensive metastatic and refractory cancer pain.

BACKGROUND: Extensive metastatic and refractory cancer pain is common, and exhibits a dissatisfactory response to the conventional intrathecal infusion of opioid analgesics. CASE PRESENTATION: The present study reports a case of an extensive metastatic esophageal cancer patient with severe intractable pain, who underwent translumbar subarachnoid puncture with intrathecal catheterization to the prepontine cistern. After continuous infusion of low-dose morphine, the pain was well-controlled with a decrease in the numeric rating scale (NRS) of pain score from 9 to 0, and the few adverse reactions to the treatment disappeared at a low dose of morphine. CONCLUSIONS: The patient achieved a good quality of life during the one-month follow-up period.

Preparation of hepatocellular carcinoma mRNA vaccines based on potential tumor targets and immunophenotypes.

Background: With the development of messenger RNA (mRNA)-based therapeutics for malignant tumor, mRNA vaccines have shown considerable promise for tumor immunotherapy. Immunophenotypes can reflect the tumor microenvironment, which might have a significant influence on the effect of immunotherapy. This study seeks to discover and validate effective antigens that can be employed to develop mRNA vaccines for hepatocellular carcinoma (HCC) and to construct immunophenotypes and immune landscapes to identify potential beneficiaries. Methods: RNA sequencing (RNASeq) data, mutation information, and clinical information were obtained from HCC patients and control cases from The Cancer Genome Atlas - Liver Hepatocellular Carcinoma (TCGA-LIHC), International Cancer Genome Consortium - Liver Cancer (ICGC-LIRI) and Gene Expression Omnibus (GEO) cohorts. Gene Expression Profiling Interactive Analysis (GEPIA2.0), cBioPortal for Cancer Genomics (cBioPortal), Tumor IMmune Estimation Resource (TIMER2.0), and immunohistochemistry (IHC) were employed to discover tumor antigens. ConsensusClusterPlus was employed to perform consistency matrix building and immunophenotypic clustering. Single sample gene set enrichment analysis (ssGSEA), ESTIMATE and monocle2 were employed to map immune cell distribution. Weighted correlation network analysis (WGCNA) was employed to identify potential gene modules that influence the efficacy of mRNA vaccines. Results: Six antigen targets were discovered in the TCGA cohort, including AURKA, CDC25C, KPNA2, MCM3, NEK2 and TUBG1, which were associated with antigen-presenting cell infiltration and poor prognosis. IHC scores of AURKA, CDC25C and MCM3 were higher in tumor tissues, and high scores of AURKA and CDC25C indicated poor prognosis in the validation cohort. Five immunophenotypes derived from TCGA-LIHC and ICGC-LIRI cohorts were consistent. Furthermore, increased expression of blue and black modules may reduce vaccine responsiveness. Conclusions: AURKA, CDC25C, KPNA2, MCM3, NEK2 and TUBG1 may be potential targets for mRNA vaccine development for HCC, especially AURKA and CDC25C. HCC patients with IS1 and IS5 subtypes perhaps present an autoimmunosuppressed state, then IS2 and IS3 subtypes perhaps the potential beneficiaries.

RAD21: A Key Transcriptional Regulator in the Development of Residual Liver Cancer.

Objective: Thermal ablation is a commonly used therapy for hepatocellular carcinoma (HCC). Nevertheless, inadequate ablation can lead to the survival of residual HCC, potentially causing rapid progression. The underlying mechanisms for this remain unclear. This study explores the molecular mechanism responsible for the rapid progression of residual HCC. Methods: We established an animal model of inadequate ablation in BALB/c nude mice and identified a key transcriptional regulator through high-throughput sequencing. Subsequently, we conducted further investigations on RAD21. We evaluated the expression and clinical significance of RAD21 in HCC and studied its impact on HCC cell function through various assays, including CCK-8, wound healing, Transwell migration and invasion. In vitro experiments established an incomplete ablation model verifying RAD21 expression and function. Using ChIP-seq, we determined potential molecules regulated by RAD21 and investigated how RAD21 influences residual tumor development. Results: High RAD21 expression in HCC was confirmed and correlated with low tumor cell differentiation, tumor growth, and portal vein thrombosis. Silencing RAD21 inhibited the migration, invasion, and proliferation significantly in liver cancer cells. Patients with high RAD21 levels showed elevated multiple inhibitory immune checkpoint levels and a lower response rate to immune drugs. Heat treatment intensified the malignant behavior of liver cancer cells, resulting in increased migration, invasion, and proliferation. After subjecting it to heat treatment, the results indicated elevated RAD21 levels in HCC. Differentially expressed molecules regulated by RAD21 following incomplete ablation were primarily associated with the VEGF signaling pathway, focal adhesion, angiogenesis, and hepatocyte growth factor receptor signaling pathway etc. Conclusion: The upregulation of RAD21 expression after incomplete ablation may play a crucial role in the rapid development of residual tumors and could serve as a novel therapeutic target.