Redox potential model for guiding moderate oxidation of polycyclic aromatic hydrocarbons in soils.

In-situ chemical oxidation is an important approach to remediate soils contaminated with persistent organic pollutants, e.g., polycyclic aromatic hydrocarbons (PAHs). However, massive oxidants are added into soils without an explicit model for predicting the redox potential (Eh) during soil remediation, and overdosed oxidants would pose secondary damage by disturbing soil organic matter and acidity. Here, a soil redox potential (Eh) model was first established to quantify the relationship among oxidation parameters, crucial soil properties, and pollutant elimination. The impacts of oxidant types and doses, soil pH, and soil organic carbon contents on soil Eh were systematically clarified in four commonly used oxidation systems (i.e., KMnO4, H2O2, fenton, and persulfate). The relative error of preliminary Eh model was increased from 48-62% to 4-16% after being modified with the soil texture and dissolved organic carbon, and this high accuracy was verified by 12 actual PAHs contaminated soils. Combining the discovered critical oxidation potential (COP) of PAHs, the moderate oxidation process could be regulated by the guidance of the soil Eh model in different soil conditions. Moreover, the product analysis revealed that the hydroxylation of PAHs occurred most frequently when the soil Eh reached their COP, providing a foundation for further microorganism remediation. These results provide a feasible strategy for selecting oxidants and controlling their doses toward moderate oxidation of contaminated soils, which will reduce the consumption of soil organic matter and protect the main structure and function of soil for future utilization. ENVIRONMENTAL IMPLICATIONS: This study provides a novel insight into the moderate chemical oxidation by the Eh model and largely reduces the secondary risks of excessive oxidation and oxidant residual in ISCO. The moderate oxidation of PAHs could be a first step to decrease their toxicity and increase their bioaccessibility, favoring the microbial degradation of PAHs. Controlling the soil Eh with the established model here could be a promising approach to couple moderate oxidation of organic contaminants with microbial degradation. Such an effective and green soil remediation will largely preserve the soil's functional structure and favor the subsequent utilization of remediated soil.

[Risk Factors and the Effect of Antiviral Prophylaxis for Herpes Zoster in Multiple Myeloma Patients].

OBJECTIVE: To study the incidence and risk factors of herpes zoster in patients with multiple myeloma and to evaluate the preventive effect of antiviral therapy. METHODS: The clinical features of multiple myeloma patients with herpes zoster were retrospectively analyzed, the risk factors of herpes zoster and the effect of antiviral prophylaxis were analyzed. RESULTS: Among 180 patients with multiple myeloma, 23 cases developed herpes zoster (12.8%). The incidence of herpes zoster was 19.1% in patients with renal dysfunction and 23.5% after autologous hematopoietic stem cell transplantation (ASCT). The incidence of herpes zoster was higher in patients receiving bortezomib-containing regimens (21/137, 15.3%) than that in those without bortezomib (2/43, 4.7%), but there was no statistical difference (P =0.067). Antiviral prophylaxis was associated with fewer zoster infections, 8/111(7.2%) developed herpes zoster in patients who received antiviral prophylaxis, and 15/69 (21.7%) in those receiving no prophylaxis(P =0.005). 65.2% of patients with herpes zoster did not receive antiviral prophylaxis. Multivariate analysis showed that bortezomib treatment, AHSCT and renal dysfunction were independent risk factors for multiple myeloma with herpes zoster, while antiviral prophylaxis was independently associated with reducing the risk of herpes zoster. Herpes zoster had no effect on OS in patients with multiple myeloma. CONCLUSION: The risk of herpes zoster in multiple myeloma patients was increased. Antiviral prophylaxis can reduce the risk of herpes zoster in patients on bortezomib-based therapy.

First Report of Fusarium luffae Causing Leaf Blight on Loquat in Eastern China.

During May-June 2021 and 2022, leaf blight symptoms were observed on loquat leaves (Eriobotrya japonica cv. 'Mogi') in Jiangsu Province (Xuzhou municipality, 117.17° E, 34.13° N) in China. Approximately 10% of the leaves on the two hundred trees studied in a six-year-old loquat orchard exhibited round lesions that changed from light yellow to reddish-brown in 8-10 days. Approximately 3% of the infected leaves exhibited numerous lesions that coalesced, leading to expansive blighted areas. Twenty-five samples of symptomatic tissue, approximately 0.2 cm2 in size, were collected in May 2022 from five different trees (five samples per tree), sterilized in 2% NaOCl for 1 min, washed twice with sterilized ddH2O, and incubated at 26°C for 5 days on PDA medium containing 50 µg/mL chloramphenicol. Six isolates were obtained via single spore isolation. ITS (OQ954852-OQ954857), TUB2 (OQ968488-OQ968493), EF1-α (OQ971890-OQ971895), RPB1 (OQ971896-OQ971901), and RPB2 (OR037266-OR037271) genes were amplified using the ITS1/ITS4, T1/T22, EF1-728F/EF1-986R, RPB1-R8/RPB1-F5, and fRPB2-7CF/fRPB2-11aR primers, respectively (O'Donnell et al. 2010). The species was identified using the Fusarioid ID database (Crous et al. 2021), revealing that all obtained isolates showed high homology to representative F. luffae strains. Upon combining the ITS, TUB2, EF1-α, RPB1, and RPB2 sequences, the isolates showed 99.42%-97.85% and 99.59%-98.10% identity to F. luffae CGMCC 3.19497 (ex-type strain) and NRRL 32522, respectively. A molecular phylogenetic tree was constructed using MEGA X, with a selection of representative Fusarium strains. Microscope observations showed septate mycelium, microconidia (6.86 ± 0.91 µm length, 1.67 ± 0.24 µm width, containing 1 septum; number of observations = 21), fusiform macroconidia (15.88 ± 1.43 µm length, 1.66 ± 0.24 µm width, containing 1 septum; number of observations = 45), and linear chlamydospores (79.36 ± 28.36 µm length, 12.03 ± 3.37 µm width; number of observations = 152). These observations are consistent with the morphology of F. luffae (Wang et al. 2019). All isolates exhibited identical morphological characteristics. All isolates were evaluated for pathogenicity in vivo using healthy non-detached loquat leaves. A total of 15 leaves from 5 different three-month-old 'Mogi' loquat trees were used for each isolate. Experiments were performed three times. A suspension of 1 × 106 spores/mL obtained from a seven-day-old colony (10 mL per 15 leaves), was sprayed on non-wounded leaves for inoculation. Sterilized ddH2O was used in the control experiment. Inoculated trees were stored at 26°C and 70% relative humidity for four days. Leaf blight symptoms were observed in all inoculated leaves, and the symptoms were observed in all repeated trials. The pathogen was recovered, and its identity was confirmed by ITS sequencing and morphological analysis, fulfilling Koch's postulates. In recent years, F. luffae has been reported to cause fruit rot on muskmelon, flower rot on kiwifruit, soybean pod rot, and leaf spot on cherry in China (Yu et al. 2022; Zhang et al. 2022; Zhao et al. 2022; Zhou et al. 2022), demonstrating the host promiscuity of this pathogen. Although F. solani has been identified as the causal agent of root rot and fruit rot on loquat (Abbas et al. 2017; Wu et al. 2021), this is the first report of F. luffae causing leaf blight on loquat worldwide. This report will help to understand the pathogens affecting loquat orchards in China.

Computed Tomography and Magnetic Resonance Imaging Findings Contribute to Differentiating Solid- and Nonsolid-Type Adenoid Cystic Carcinoma in Maxillary Sinus.

PURPOSE: This study aimed to evaluate the imaging features of maxillary sinus adenoid cystic carcinoma (ACC) on computed tomography (CT) and magnetic resonance imaging (MRI) and to investigate the imaging differences between solid and nonsolid maxillary sinus ACC. METHODS: We retrospectively reviewed 40 cases of histopathologically confirmed ACC of the maxillary sinus. All the patients underwent CT and MRI. Based on the histopathological characteristics, the patients were classified into 2 groups: ( a ) solid maxillary sinus ACC (n = 16) and ( b ) nonsolid maxillary sinus ACC (n = 24). Imaging features such as tumor size, morphology, internal structure, margin, type of bone destruction, signal intensity, enhancement changes, and perineural tumor spread on CT and MRI, were evaluated. The apparent diffusion coefficient (ADC) was measured. Comparisons of imaging features and ADC values were performed between the solid and nonsolid maxillary sinus ACC using χ 2 and nonparametric tests. RESULTS: The internal structure, margin, type of bone destruction, and degree of enhancement significantly differed between solid and nonsolid maxillary sinus ACC (all P < 0.05). The ADC of the solid maxillary sinus ACC was considerably lower than that of the nonsolid maxillary sinus ( P < 0.05). CONCLUSIONS: Computed tomography and MRI may aid in the differentiation of solid and nonsolid types of maxillary sinus ACC.

Refining eligibility criteria of unit selection for myeloablative cord blood transplantation in acute leukemia: Real-world experience of a referral center.

The algorithm for cord blood (CB) unit selection is still somewhat ambiguous. We retrospectively analyzed 620 cases of acute leukemia between 2015 and 2020, who were treated with myeloablative single-unit umbilical CB transplantation (UCBT). We found that, when human leukocyte antigen (HLA) mismatch was ≤3/10, CD34+ cell dosage <0.83 × 105/kg-considerably lower than prevalent guidelines-was permissible without affecting survival. Moreover, synergy between donor killer-cell immunoglobulin-like receptors (KIR) haplotypes-B and donor-recipient HLA-C mismatch protected against relapse-related mortality. We submit that minimum required CD34+ cell dosage can possibly be relaxed to broaden access to UCBT, and donor KIR genotyping should be considered during unit selection.

Impact of Iron Overload and Iron Chelation with Deferasirox on Outcomes of Patients with Severe Aplastic Anemia after Allogeneic Hematopoietic Stem Cell Transplantation.

Patients suffering from severe aplastic anemia (SAA) need frequent blood transfusions during allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, these transfusions can result in an excess of iron in the body tissues, which can negatively impact the success of transplantation. This study aimed to examine the impact of pretransplantation iron overload (IO) on the outcomes of allo-HSCT in patients with SAA. It also investigated whether iron chelation (IC) therapy is necessary to enhance transplantation outcomes in SAA patients by providing guidelines for determining when excess iron should be chelated. The study consisted of 2 parts. In cohort 1, which was retrospective and conducted from April 2012 to December 2018, SAA patients receiving their first allo-HSCT were divided into 2 groups based on their pretransplantation serum ferritin (SF) level: the IO group (SF >1000 ng/mL; n = 17) and the non-IO group (SF ≤1000 ng/mL; n = 48). Cohort 2, a prospective clinical trial conducted from January 2019 to July 2020, included SAA patients diagnosed with IO who were treated with IC therapy using deferasirox at a dose of 10 to 30 mg/kg. Patients were separated into 2 groups based on their pretransplantation SF level: the IC success (ICsuccess) group (SF ≤1000 ng/mL; n = 18) and the IC failure (ICfailure) group (SF >1000 ng/mL; n = 28). All participants were evaluated for the correlation between pretransplantation SF level and transplantation outcomes. A P value <.05 was considered statistically significant. There was no significant difference in the speed of engraftment among the 3 cell lineages or in the incidence of 100-day grade II-IV acute graft-versus-host disease (aGVHD), grade III-IV aGVHD, or 3-year chronic GVHD between the 2 groups in both cohorts. Of note, however, in cohort 1, both 1-year overall survival (OS) (41.2% versus 83.3%; P < .001) and 3-year OS (35.3% versus 83.3%; P < .001) were significantly worse in the IO group. Furthermore, 180-day transplantation related mortality (TRM) (47.1% versus 14.6%; P = .005) and 1-year TRM (52.9% versus 16.7%; P = .002) were significantly higher in the IO group. The IO group was significantly associated with inferior 3-year OS in both univariate and multivariate analyses. In cohort 2, 1-year OS (88.9% versus 42.9%; P = .003) and 3-year OS (83.3% versus 42.9%; P = .007) were significantly better in the ICsuccess group, whereas 180-day TRM (11.1% versus 39.3%; P = .040) and 1-year TRM (11.1% versus 57.1%; P = .003) were significantly lower in the ICsuccess group. These differences were confirmed in both univariate and multivariate analyses. This study involving 2 cohorts shows that pre-HSCT IO has a negative impact on transplantation outcomes in SAA patients. Chelating excess iron with an SF level <1000 ng/mL was found to be necessary and could potentially improve the outcomes.

Predicting laterite redox potential with iron activity and electron transfer term.

Predicting the redox behavior of organic contaminants and heavy metals in soils is challenging because there are few soil redox potential (Eh) models. In particular, current aqueous and suspension models usually show a significant deviation for complex laterites with few Fe(II). Here, we measured the Eh of simulated laterites over a range of soil conditions (2450 tests). The impacts of soil pH, organic carbon, and Fe speciation on the Fe activity were quantified as Fe activity coefficients, respectively, using a two-step Universal Global Optimization method. Integrating these Fe activity coefficients and electron transfer terms into the formula significantly improved the correlation of measured and modeled Eh values (R2 = 0.92), and the estimated Eh values closely matched the relevant measured Eh values (accuracy R2 = 0.93). The developed model was further verified with natural laterites, presenting a linear fit and accuracy R2 of 0.89 and 0.86, respectively. These findings provide compelling evidence that integrating Fe activity into the Nernst formula could accurately calculate the Eh if the Fe(III)/Fe(II) couple does not work. The developed model could help to predict the soil Eh toward controllable and selective oxidation-reduction of contaminants for soil remediation.

First report of jujube anthracnose caused by Colletotrichum siamense in China.

Jujube (Zizyphus jujuba Mill.), a native small deciduous tree of China, is widely cultivated in China, Korea, India, Japan, Europe, and the United States (Chen et al. 2020). The fruit have been commonly consumed as healthy food supplements and traditional Chinese medicine for over 2000 years (Li et al. 2007). In August 2019, anthracnose-like leaf spot symptoms were observed on jujube plants in Xiaomenya Village, Jinan City, Shandong Province, China (36°27'39″N, 117°3'13″E), with over 30% leaf disease incidence. The spots were circular, sunken, brown in the center and with dark brown edges. As the spots enlarged and coalesced, it resulted in leaf perforation and early defoliation. Sometimes acervuli were observed on the lesions (Fig. S1a, b). To identify the causal agent, 20 diseased leaves were sampled, the margins of the lesions were cut into pieces (5 × 5 mm), sterilized and cultured following the protocol described previously (Wan et al. 2020) at 25 ℃ for 5 days. Twelve monospore isolates showing identical colony morphology were obtained. Three representative isolates, JNZG11, JNZG311, JNZG313, were used for further study. When grown on PDA the colony color was initially white and then turned pale-gray to gray in 5-day-old cultures. On the reverse, colonies were brown-black with an orange pigmentation near the center. Aerial mycelium was cottony, dense, white to pale-gray. Conidia were hyaline, 1-celled, smooth-walled, subcylindrical, oblong, attenuated with slightly rounded ends, (11.1-) 12.7-13.3 (-17.8) ×(-4.4) 5.2-5.5 (-6.3) µm (n=50). Appressoria were dark-brown, oval or irregular, (7.3-) 8.6-9.2 (-9.8) ×(-5.1) 5.8-6.9 (-7.0) µm (n=50) (Fig. S1c-g). The morphology resembled those of Colletotrichum gloeosporioides species complex (Cannon et al. 2012). For accurate identification, the sequences of the ribosomal internal transcribed spacer (ITS), actin (ACT), ß-tub2 (TUB2), calmodulin (CAL), chitin synthase (CHS-1), and glyceraldehyde-3phosphate dehydrogenase (GAPDH) of the 3 isolates were sequenced (Weir et al. 2012), and deposited into GenBank (Accession Nos. see Table 1). The six loci (ITS, GAPDH, ACT, CHS-1, CAL, and TUB2) were concatenated and the aligned sequences (1904 bp) were 99.7% homologous to ex-type C. siamense ICMP18578. The sequences of 38 Colletotrichum species (44 isolates) were downloaded from GenBank for phylogenetic analyses. In the maximum likelihood phylogenetic tree generated, the highest log likelihood was -8798.90 and the three isolates were all in the C. siamense clade (bootstrap support 94 %) (Fig. S2). To complete Koch's postulates, 60 healthy, mature jujube leaves on 12 branches (5 leaves per branch) (variety 'Zhongqiuhong') were inoculated with 20 µL of spore suspension (106 conidia/mL) or sterile water as a control. The branches were placed in sterile beakers containing a small amount of sterile water sealed with plastic wrap and maintained at 28 °C, 12 h light/dark. Five days after inoculation, all treated leaves showed the typical anthracnose symptom, similar to that observed in the field (Fig. S1h). The same fungus was re-isolated from the margins of the lesions using the aforementioned methods. Whereas no fungus were isolated from the controls. Previously, C. siamense has been reported to infect Z. mauritiana in China (Shu et al. 2020). To our knowledge, this is the first report of C. siamense causing anthracnose on Z. jujuba in China. This finding provides crucial information for the effective management of this disease.

The Composite Immune Risk Score predicts overall survival after allogeneic hematopoietic stem cell transplantation: A retrospective analysis of 1838 cases.

There has been little consensus on how to quantitatively assess immune reconstitution after hematopoietic stem cell transplantation (HSCT) as part of the standard of care. We retrospectively analyzed 11 150 post-transplant immune profiles of 1945 patients who underwent HSCT between 2012 and 2020. 1838 (94.5%) of the cases were allogeneic HSCT. Using the training set of patients (n = 729), we identified a composite immune signature (integrating neutrophil, total lymphocyte, natural killer, total T, CD4+ T, and B cell counts in the peripheral blood) during days 91-180 after allogeneic HSCT that was predictive of early mortality and moreover simplified it into a formula for a Composite Immune Risk Score. When we verified the Composite Immune Risk Score in the validation (n = 284) and test (n = 391) sets of patients, a high score value was found to be associated with hazard ratios (HR) of 3.64 (95% C.I. 1.55-8.51; p = .0014) and 2.44 (95% C.I., 1.22-4.87; p = .0087), respectively, for early mortality. In multivariate analysis, a high Composite Immune Risk Score during days 91-180 remained an independent risk factor for early mortality after allogeneic HSCT (HR, 1.80; 95% C.I., 1.28-2.55; p = .00085). In conclusion, the Composite Immune Risk Score is easy to compute and could identify the high-risk patients of allogeneic HSCT who require targeted effort for prevention and control of infection.

Automatic identification of harmful algae based on multiple convolutional neural networks and transfer learning.

The monitoring of harmful phytoplankton is very important for the maintenance of the aquatic ecological environment. Traditional algae monitoring methods require professionals with substantial experience in algae species, which are time-consuming, expensive, and limited in practice. The automatic classification of algae cell images and the identification of harmful phytoplankton images were realized by the combination of multiple convolutional neural networks (CNNs) and deep learning techniques based on transfer learning in this work. Eleven common harmful and 31 harmless phytoplankton genera were collected as input samples; the five CNNs classification models of AlexNet, VGG16, GoogLeNet, ResNet50, and MobileNetV2 were fine-tuned to automatically classify phytoplankton images; and the average accuracy was improved 11.9% when compared to models without fine-tuning. In order to monitor harmful phytoplankton which can cause red tides or produce toxins severely polluting drinking water, a new identification method of harmful phytoplankton which combines the recognition results of five CNN models was proposed, and the recall rate reached 98.0%. The experimental results validate that the recognition performance of harmful phytoplankton could be significantly improved by transfer learning, and the proposed identification method is effective in the preliminary screening of harmful phytoplankton and greatly reduces the workload of professional personnel.

Phase 1 multicenter, dose-expansion study of ARX788 as monotherapy in HER2-positive advanced gastric and gastroesophageal junction adenocarcinoma.

ARX788 is an anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate with AS269 as cytotoxic payload. In this phase 1 multicenter dose-expansion clinical trial, patients with HER2-positive advanced gastric/gastroesophageal junction adenocarcinoma failing to respond to prior trastuzumab-based standard treatment were enrolled. Between July 15th, 2019, and March 14th, 2022, 30 participants were enrolled. Twenty-eight (93.3%) patients experienced at least one drug-related adverse event (AE) and 13.3% experienced grade 3 ARX788-related AEs. The confirmed objective response rate is 37.9% (95% confidence interval [CI]: 20.7%-57.7%) and the disease control rate is 55.2% (95% CI: 35.7%-73.6%). With a median follow up of 10 months, the median progression-free survival and overall survival are 4.1 (95% CI: 1.4-6.4) and 10.7 months (95% CI: 4.8-not reached), respectively. The median duration of response is 8.4 (95% CI: 2.1-18.9) months. ARX788 is well tolerated and has promising anti-tumor activity in patients with HER2-positive advanced gastric adenocarcinoma (ChinaDrugTrials.org.cn: CTR20190639).

Impact of a super typhoon on heavy metal distribution, migration, availability in agricultural soils.

Heavy metal contamination in agricultural soils is a worldwide concerned environmental issue. However, a short-term extreme hydrodynamic event (e.g., a super typhoon) may significantly affect the distribution, migration, and availability of heavy metals in agriculture soils on a large scale. The limited understanding of such an impact prevents effective environment survey, risk assessment, and remediation strategy for heavy metal contaminated soils. Here, we show a massive migration of heavy metals during a super typhoon (Lekima) based on the field investigation, simulated experiments, and isotopic fingerprinting. The contaminations of heavy metals (Cd, Zn, Cu, Ni, Cr and As) of agricultural soils at 209 sampling sites over 3.59 × 105 km2, were significantly relieved by 10.3-42.0 % after the typhoon, because of the primary contribution of runoff erosion over interflow according to the simulated soil erosions. However, the available fractions (as % of the total amount of each metal) were metal-dependent, with Cd, Zn, Cu, and Ni increased (5.3-26.4 %), and Cr and As decreased (0.9-3.5 %). In contrary, the Pb contamination was slightly aggravated by 8.7 % after the typhoon, and the Pb isotopic signatures indicate its input and migration via wet precipitation and surface runoff. The soil properties (e.g., pH and organic matter) showed limited impact on the migration of heavy metals during this typhoon. These results suggest that a natural short-term extreme hydrodynamic event can drive the massive migration of heavy metals in agricultural soils and their trade-off with other environmental medias, providing valuable information for multi-medias environmental risk assessment and cooperative remediation that can be significantly disturbed by such an event.

Diagnostic Biomarker Hsa_circ_0126218 and Functioning Prediction in Peripheral Blood Monocular Cells of Female Patients With Major Depressive Disorder.

INTRODUCTION: Although major depressive diroder (MDD) has brought huge burden and challenges to society globally, effective and accurate diagnoses and treatments remain inadequate. The pathogenesis that for women are more likely to suffer from depression than men needs to be excavated as well. The function of circRNAs in pathological process of depression has not been widely investigated. This study aims to explore potential diagnostic biomarker circRNA of female patients with MDD and to investigate its role in pathogenesis. METHODS: First, an expression profile of circRNAs in the peripheral blood monocular cells of MDD patients and healthy peripherals were established based on high-throughput sequencing analysis. In addition, the top 10 differentially expressed circRNAs were quantified by quantitative real-time PCR to explore diagnostic biomarkers. To further investigate the function of biomarkers in the pathogenesis of MDD, bioinformatics analysis on downstream target genes of the biomarkers was carried out. RESULTS: There is a mass of dysregulated circRNAs in PBMCs between female MDD patients and healthy controls. Among the top 10 differentially expressed circRNAs, hsa_circ_0126218 is more feasible as a diagnostic biomarker. The expression level of hsa_circ_0126218 displayed upregulation in patients with MDD and the area under the operating characteristic curve of hsa_circ_0126218 was 0.801 (95% CI 0.7226-0.8791, p < 0.0001). To explain the competing endogenous RNA role of hsa_circ_0126218 in the pathogenesis of female MDD, a hsa_circ_0126218-miRNA-mRNA network was established. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses stated that some of the enriched pathways downstream of hsa_circ_0126218 are closely related to MDD. Moreover, we established a protein-protein network to further screen out the hub genes (PIK3CA, PTEN, MAPK1, CDC42, Lyn, YES1, EPHB2, SMAD2, STAT1, and ILK). The function of hsa_circ_0126218 was refined by constructing a verified circRNA-predicted miRNA-hub gene subnetwork. CONCLUSION: hsa_circ_0126218 can be considered as a new female MDD biomarker, and the pathogenesis of female MDD by the downstream regulation of hsa_circ_0126218 has been predicted. These findings may help further improve the early detection, effective diagnosis, convenient monitoring of complications, precise treatment, and timely recurrence prevention of depression.

Identification and Clinical Validation of 4-lncRNA Signature for Predicting Survival in Head and Neck Squamous Cell Carcinoma.

BACKGROUND: The prognosis of patients with head and neck squamous cell carcinoma (HNSCC) is still poor due to the lack of effective prognostic biomarkers. lncRNA is an important survival prognostic indicator and has important biological functions in tumorigenesis. METHODS: RNA-seq was re-annotated, and comprehensive clinical information was obtained from the GEO database. Univariate and multivariate Cox regression analyses were used to construct the lncRNA prognosis signature. Gene set enrichment analysis (GSEA) enrichment analysis method is used to explore the possible mechanism of the selected lncRNA influencing HNSCC development. The rms package was used to calculate the C-index to evaluate the overall prediction performance between different signature. PCR is used to detect the expression of selected lncRNA in cancer and adjacent tissues. RESULTS: In the GSE65858 training cohort, 124 probes significantly related to prognosis were identified, 11 significant lncRNAs were further selected by rbsurv dimensionality reduction analysis. Finally, 4-lncRNA signature was constructed by multivariate Cox analysis. This signature was associated with tumor-associated pathway and is an independent factor of the patient's prognosis. 4-lncRNA signature has strong robustness and can exert stable prediction performance in different cohorts. A nomogram comprising the prognostic model to predict the overall survival was established. The 4-lncRNA signature was significantly upregulated in HNSCC samples. CONCLUSION: The predictive model and nomogram will enable patients to be more accurately managed in trials and clinical practices and could be applied as a new prognostic model for predicting survival of HNSCC patients.

Nonclinical Development of Next-generation Site-specific HER2-targeting Antibody-drug Conjugate (ARX788) for Breast Cancer Treatment.

Conventional antibody-drug conjugates (ADC) utilize native surface-exposed lysines or cysteines on the antibody of interest to conjugate cytotoxic payload. The nonspecific conjugation results in a mixture with variable drug-to-antibody ratios (DAR), conjugation sites, and ADCs that are often unstable in systemic circulation. ARX788 is an ADC consisting of a HER2-targeting antibody site-specifically conjugated with a potent antitubulin cytotoxic drug-linker, AS269. The site-specific conjugation is achieved by first incorporating the nonnatural amino acid, para-acetyl phenylalanine (pAF), into the antibody, followed by covalent conjugation of AS269 to the pAF to form a highly stable oxime bond resulting in a DAR 2 ADC. ARX788 exhibits significant, dose-dependent antitumor activity against HER2- expressing breast and gastric xenograft tumors. Pharmacokinetic (PK) studies in multiple species showed the highly stable nature of ARX788 with overlapping PK profiles for the intact ADC and total antibody. Metabolism studies demonstrated that pAF-AS269 was the sole major metabolite of ARX788, with no evidence for the release of free drug often observed in conventional ADCs and responsible for adverse side effects. Furthermore, ARX788 demonstrated a favorable safety profile in monkeys with a highest nonseverely toxic dose of 10 mg/kg, which was well above the efficacious dose level observed in preclinical tumor models, thus supporting clinical development of ARX788.

The Correlation and Influencing Factors of Crisis Response Ability and Psychological Factors in Patients with Liver Cirrhosis.

BACKGROUND: Illness can provoke a crisis response that affects condition acceptance, treatment and recovery. Patients' sense of coherence can influence this explored across patient cohorts internationally. However, few studies examine these effects in patients with hepatic cirrhosis. This study investigated sense of coherence and social support of patients with hepatic cirrhosis. METHODS: The psychological status of 146 patients admitted to the Digestive System Department, First Affiliated Hospital of Harbin Medical University, Harbin, China from Mar 2016 to Mar 2019 with hepatic cirrhosis was assessed using the Sense of Coherence (SOC-13), Social Support Rating Scale (SSRS) and crisis assessment scales. RESULTS: There was a low level of crisis response in patients with hepatic cirrhosis that was influenced by age, disease course, education level and Child-Pugh grade and negatively correlated with sense of coherence and social support. CONCLUSION: Liver cirrhosis patients had a low level of crisis response. As the level of crisis response in is correlated with patients' sense of coherence, social support and educational level, careful assessment, tailored educational interventions and mobilizing of family support are important to maximize responses to illness and thus improve quality of life.

Effect of phosphate on amorphous iron mineral generation and arsenic behavior in paddy soils.

Arsenic (As) contamination was detected in paddy soils of Guangdong, China due to mining and weathering processes. Furthermore, As may be released into the soil and irrigation water during the application of phosphate (P). In this study, As behavior was assessed in three paddy soils (S6, S8 and TR) along the Hengshi river using batch and circular flow experiments with different phosphate application doses (0, 1, 5, 10, 50, 100 mg/L). The results indicate that pH variation (3-7) and higher phosphate concentrations in solution, can induce the release of As, with total As release ranked in the order: S6 > S8 > TR. In addition, AsV was the main state affected by phosphate in the circular soil solution. In particular, after 7 days of P10 application, the highest As concentration in S6, S8 and TR soil solutions reached 2298.4, 829.9 and 153.9 µg/L respectively, with the AsV state accounting for 93%, 97% and 18% of As. Some minerals were found to be generated in the middle container, most of which were amorphous iron or aluminum oxides and hydroxides, as confirmed by XRD. With mineral generation, the As concentration in soil solutions decreased to 314.2, 98.1 and 34.1 µg/L. The SEM results indicate that the minerals became more fine (<100 nm) when more P was applied. In addition, XPS, SEM-eds and elemental analysis results also revealed that As distribution was closely associated with iron minerals. Along with soil depth, P influenced the state and distribution of iron minerals and As in the topsoil, while phosphate increased the available As and reduced the amorphous iron mineral content in the soil. Therefore, it is essential to evaluate As behavior in paddy soils, to monitor and avoid potential food security risks.

Solanum nigrum polysaccharide inhibits tumor growth in H22-bearing mice through regulation of caspase-3 and bcl-2.

OBJECTIVE: The objective of this study was to investigate the effect of Solanum nigrum polysaccharides (SNPs) on tumor growth in H22 hepatocarcinoma cells bearing mice and explore the mechanism by focusing on the regulation of the expression of caspase-3 and bcl-2. MATERIALS AND METHODS: Totally, 50 mice bearing with H22 cells were randomly divided into five groups: Model group, cyclophosphamide group (CTX, 30 mg/kg), SNP groups with low, medium, and high doses of SNP (30, 60, and 120 mg/kg). Twenty-four hours after inoculation of H22 cells, CTX or SNP were given by gavage once a day for 10 days. The growth of tumor was observed. The tumor inhibition rate, indexes of the spleen and thymus were calculated. The immunohistochemical method was used for the determination of caspase-3 and bcl-2 expression in the tumor tissue. RESULTS: SNP (30, 60, and 120 mg/kg) reduced the average tumor weight compared with that in model group in a dose-dependent manner, and the tumor inhibition rates were 37.73%, 38.24%, and 42.60%, respectively. In addition, SNP dose dependently increased the index of the thymus compared with that of the CTX group. Immunohistochemistry results showed that the protein expression of caspase-3 in SNP groups was higher, but the expression of bcl-2 was lower than that in model group in a dose-dependent manner. CONCLUSION: SNP inhibited the growth of tumor in H22-bearing mice and protected the immune organ. The mechanism underlying the inhibition of tumor might be related to the upregulation of caspase-3 and downregulation of bcl-2.

Gynostemosides A-E, megastigmane glycosides from Gynostemma pentaphyllum.

Megastigmane glycosides (1-5) together with seven (6-12) related known compounds were isolated from the whole plants of Gynostemma pentaphyllum. The structures were elucidated by means of spectroscopic methods, including 2D NMR, HR-ESIMS, and circular dichroism (CD), as well as chemical transformations to be (3R,4R,5S,6S,7E)-3,4,6-trihydroxymegastigmane-7-en-9-one-3-O-beta-D-glucopyranoside (gynostemoside A, 1), (3S,4S,5R,6R,7E,9R)-3,4,6,9-tetrahydroxymegastigmane-7-en-3-O-beta-D-glucopyranoside (gynostemoside B, 2), (3S,4S,5S,6S,7E,9R)-3,4,9-trihydroxymegastigmane-7-en-9-O-beta-D-glucopyranoside (gynostemoside C, 3), (3S,4S,5S,6S,7E,9R)-3,4,9-trihydroxymegastigmane-7-en-3-O-beta-D-glucopyranoside (gynostemoside D, 4), and (3S,4S,5S,6S,7E,9R)-3,4,9-trihydroxymegastigmane-7-en-4-O-beta-D-glucopyranoside (gynostemoside E, 5), respectively.