A simple way to detect disease-associated cellular molecular alterations from mixed-cell blood samples.

Blood is a promising surrogate for solid tissue to investigate disease-associated molecular biomarkers. However, proportion changes of the constituent cells in the often-used peripheral whole blood (PWB) or peripheral blood mononuclear cell (PBMC) samples may influence the detection of cell-specific alterations under disease states. We propose a simple method, Ref-REO, to detect molecular alterations in leukocytes using the mixed-cell blood samples. The method is based on the predetermined within-sample relative expression orderings (REOs) of genes in purified leukocytes of healthy people. Both the simulated and real mixed-cell blood gene expression profiles were used to evaluate the method. Approximately 99% of the differentially expressed genes (DEGs) detected by Ref-REO in the simulated mixed-cell data are owing to the transcriptional alterations in leukocytes rather than the proportion changes of leukocytes. For the real mixed-cell data, the DEGs detected by Ref-REO in the PBMCs expression data for systemic lupus erythematosus (SLE) patients overlap significantly with the DEGs detected in the expression data of SLE CD4 + T cells and B cells and they are mainly enriched with mRNA editing and interferon-associated genes. The detected DEGs in the PWB data for lung carcinoma patients are significantly enriched with coagulation-associated functional categories that are closely associated with cancer progression. In conclusion, the proposed method is capable of detecting the disease-associated leukocyte-specific molecular alterations, using mixed-cell blood samples, which provides simple, transferable and easy-to-use candidates for disease biomarkers.

Transcriptional signatures for coupled predictions of stage II and III colorectal cancer metastasis and fluorouracil-based adjuvant chemotherapy benefit.

The current study suggests that the identification of predictive signatures of fluorouracil (5-FU) response for stage II and III colorectal cancer (CRC) could be confounded by chemotherapy-irrelevant low relapse risk. Using the samples of patients with stage II and III CRC who were treated with curative surgery only, we identified a signature with which to predict chemotherapy-irrelevant relapse risk for patients after curative surgery. By applying this signature to the samples of patients with stage II and III CRC who were treated with 5-FU-based adjuvant chemotherapy (ACT) after surgery, we predicted the relapse risk if treated with surgery only. From high-risk samples, we further identified another signature with which to predict therapeutic benefit from 5-FU-based ACT. On the basis of the relative expression orderings of gene pairs, a postsurgery relapse risk signature that consisted of 44 gene pairs was developed and verified in 3 independent data sets. A 5-FU therapeutic benefit signature that consisted of 4 gene pairs was then developed to predict the response of 5-FU-based ACT for those patients with high relapse risk after curative surgery. The signature was verified in 4 independent datasets. For patients with stage II and III CRC, the coupled signatures can first identify patients with high relapse risk after curative surgery, then predict therapeutic benefit from 5-FU-based ACT.-Song, K., Guo, Y., Wang, X., Cai, H., Zheng, W., Li, N., Song, X., Ao, L., Guo, Z., Zhao, W. Transcriptional signatures for coupled predictions of stage II and III colorectal cancer metastasis and fluorouracil-based adjuvant chemotherapy benefit.

Robust transcriptional signatures for low-input RNA samples based on relative expression orderings.

BACKGROUND: It is often difficult to obtain sufficient quantity of RNA molecules for gene expression profiling under many practical situations. Amplification from low-input samples may induce artificial signals. RESULTS: We compared the expression measurements of low-input mRNA samples, from 25 pg to 1000 pg mRNA, which were amplified and profiled by Smart-seq, DP-seq and CEL-seq techniques using the Illumina HiSeq 2000 platform, with those of the paired high-input (50 ng) mRNA samples. Even with 1000 pg mRNA input, we found that thousands of genes had at least 2 folds-change of expression levels in the low-input samples compared with the corresponding paired high-input samples. Consequently, a transcriptional signature based on quantitative expression values and determined from high-input RNA samples cannot be applied to low-input samples, and vice versa. In contrast, the within-sample relative expression orderings (REOs) of approximately 90% of all the gene pairs in the high-input samples were maintained in the paired low-input samples with 1000 pg input mRNA molecules. Similar results were observed in the low-input total RNA samples amplified and profiled by the Whole-Genome DASL technique using the Illumina HumanRef-8 v3.0 platform. As a proof of principle, we developed REOs-based signatures from high-input RNA samples for discriminating cancer tissues and showed that they can be robustly applied to low-input RNA samples. CONCLUSIONS: REOs-based signatures determined from the high-input RNA samples can be robustly applied to samples profiled with the low-input RNA samples, as low as the 1000 pg and 250 pg input samples but no longer stable in samples with less than 250 pg RNA input to a certain degree.

Statistically controlled identification of differentially expressed genes in one-to-one cell line comparisons of the CMAP database for drug repositioning.

BACKGROUND: The Connectivity Map (CMAP) database, an important public data source for drug repositioning, archives gene expression profiles from cancer cell lines treated with and without bioactive small molecules. However, there are only one or two technical replicates for each cell line under one treatment condition. For such small-scale data, current fold-changes-based methods lack statistical control in identifying differentially expressed genes (DEGs) in treated cells. Especially, one-to-one comparison may result in too many drug-irrelevant DEGs due to random experimental factors. To tackle this problem, CMAP adopts a pattern-matching strategy to build "connection" between disease signatures and gene expression changes associated with drug treatments. However, many drug-irrelevant genes may blur the "connection" if all the genes are used instead of pre-selected DEGs induced by drug treatments. METHODS: We applied OneComp, a customized version of RankComp, to identify DEGs in such small-scale cell line datasets. For a cell line, a list of gene pairs with stable relative expression orderings (REOs) were identified in a large collection of control cell samples measured in different experiments and they formed the background stable REOs. When applying OneComp to a small-scale cell line dataset, the background stable REOs were customized by filtering out the gene pairs with reversal REOs in the control samples of the analyzed dataset. RESULTS: In simulated data, the consistency scores of overlapping genes between DEGs identified by OneComp and SAM were all higher than 99%, while the consistency score of the DEGs solely identified by OneComp was 96.85% according to the observed expression difference method. The usefulness of OneComp was exemplified in drug repositioning by identifying phenformin and metformin related genes using small-scale cell line datasets which helped to support them as a potential anti-tumor drug for non-small-cell lung carcinoma, while the pattern-matching strategy adopted by CMAP missed the two connections. The implementation of OneComp is available at https://github.com/pathint/reoa . CONCLUSIONS: OneComp performed well in both the simulated and real data. It is useful in drug repositioning studies by helping to find hidden "connections" between drugs and diseases.

Evaluating hepatocellular carcinoma cell lines for tumour samples using within-sample relative expression orderings of genes.

BACKGROUND & AIMS: Concerns are raised about the representativeness of cell lines for tumours due to the culture environment and misidentification. Liver is a major metastatic destination of many cancers, which might further confuse the origin of hepatocellular carcinoma cell lines. Therefore, it is of crucial importance to understand how well they can represent hepatocellular carcinoma. METHODS: The HCC-specific gene pairs with highly stable relative expression orderings in more than 99% of hepatocellular carcinoma but with reversed relative expression orderings in at least 99% of one of the six types of cancer, colorectal carcinoma, breast carcinoma, non-small-cell lung cancer, gastric carcinoma, pancreatic carcinoma and ovarian carcinoma, were identified. RESULTS: With the simple majority rule, the HCC-specific relative expression orderings from comparisons with colorectal carcinoma and breast carcinoma could exactly discriminate primary hepatocellular carcinoma samples from both primary colorectal carcinoma and breast carcinoma samples. Especially, they correctly classified more than 90% of liver metastatic samples from colorectal carcinoma and breast carcinoma to their original tumours. Finally, using these HCC-specific relative expression orderings from comparisons with six cancer types, we identified eight of 24 hepatocellular carcinoma cell lines in the Cancer Cell Line Encyclopedia (Huh-7, Huh-1, HepG2, Hep3B, JHH-5, JHH-7, C3A and Alexander cells) that are highly representative of hepatocellular carcinoma. Evaluated with a REOs-based prognostic signature for hepatocellular carcinoma, all these eight cell lines showed the same metastatic properties of the high-risk metastatic hepatocellular carcinoma tissues. CONCLUSIONS: Caution should be taken for using hepatocellular carcinoma cell lines. Our results should be helpful to select proper hepatocellular carcinoma cell lines for biological experiments.

Assessment of the antimicrobial and immunomodulatory activity of QS-CATH, a promising therapeutic agent isolated from the Chinese spiny frogs (Quasipaa spinosa).

Cathelicidins are important antimicrobial peptides in various vertebrate species where they are crucial parts of the innate immune system. The current understanding of amphibian cathelicidins is limited, particularly with regard to their immunomodulatory effects. To address this knowledge gap, we produced the cDNA sequence of the cathelicidin gene from a skin transcriptome of the Chinese spiny frog Quasipaa spinosa. The amino acid sequence of the Quasipaa spinosa cathelicidin (QS-CATH) was predicted to consist of a signal peptide, a cathelin domain, and a mature peptide. Comparative analysis of the QS-CATH amino acid sequence with that of other amphibian cathelicidins revealed high variability in the functional mature peptide among amphibians, whereas the cathelin domain was conserved. The QS-CATH gene was expressed in several tissues, with the highest level of expression in the spleen. Upregulation of QS-CATH after Aeromonas hydrophila infection occurred in the kidney, gut, spleen, skin, and liver. Chemically synthesized QS-CATH exhibited pronounced antibacterial activity against Shigella flexneri, Staphylococcus warneri, Escherichia coli, Salmonella enterica, and Listeria monocytogenes. Furthermore, QS-CATH disrupted the cell membrane integrity of S. flexneri, as evidenced by a lactate dehydrogenase release assay, and it hydrolyzed the genomic DNA of S. flexneri. Additionally, QS-CATH elicited chemotaxis and modulated the expression of inflammatory cytokine genes in RAW264.7 mouse leukemic monocyte/macrophage cells. These findings confirm the antimicrobial effects of amphibian cathelicidin and its ability to influence immune cell function. This will expedite the potential utilization of amphibian antimicrobial peptides as therapeutic agents.

Evaluating screw-shaft pile composite foundations in round Gravelly soil: A study using model tests and numerical simulations.

Screw-shaft piles have seen extensive adoption in construction and railroad engineering, due to their superior enhanced bearing capacity and cost-effectiveness. While monopiles have been thoroughly examined, composite foundations that include screw-shaft piles have not been studied as extensively. Proper determination of geometric parameters for both the piles and the cushion is a critical aspect of successful design. This paper introduces a comprehensive examination that merges indoor experiments with numerical simulations, aiming to evaluate the bearing capacity, settlement characteristics, and force characteristics of screw-shaft piles under a variety of conditions. This study scrutinizes key components, such as root diameter, pitch, cushion modulus, and the threaded portion's proportion. The research outcomes offer crucial insights for optimizing the design parameters of screw-shaft pile composite foundations. The results indicate that the side resistance of screw-shaft piles initially increases with the threaded section's length, stabilizing at an optimal length of approximately 0.44-0.55 times the pile length (L). Furthermore, although decreasing the pitch improves bearing capacity, it also introduces variations in pile material usage, with optimal bearing performance noted at a pitch approximately equal to the diameter (D). Moreover, screw-shaft piles with thread widths ranging between 0.58D and 0.67D show a significant decrease in stress concentrations, approximately 22 % less than those with a width of 0.5D. By setting the cushion modulus within the 40 MPa-60 MPa range, reduced settlement and optimal pile-soil stress ratios were achieved. These research outcomes provide critical insights into optimizing screw-shaft pile composite foundation design parameters, serving as valuable guidance for designers and engineers in diverse civil engineering projects.

Prominent Vessel Signs After Endovascular Thrombectomy Corelates with Unexplained Neurological Deterioration and is a More Reliable Imaging Predictor of Prognosis in Anterior Large Vessel Occlusion Stroke.

OBJECTIVE: Fifty percent of patients who undergo endovascular thrombectomy (EVT) for large-vessel occlusion exhibit unfavorable outcomes. The primary factor is attributed to persistent brain impairment even after successful EVT. The prominent vessel sign (PVS) on magnetic resonance susceptibility-weighted imaging reflects the territory of dysmetabolism and may facilitate an expeditious assessment for prognostication. We aimed to examine the relationship between PVS after EVT and the occurrence of early neurological deterioration (END) and 3-month outcomes. METHODS: Patients who underwent EVT and multimodal magnetic resonance imaging were included. END was defined as an increase of ≥2 in the National Institutes of Health Stroke Scale within 72 hours after EVT. Symptomatic intracranial hemorrhage, malignant edema, and surgical complications were defined as definite END, whereas the other symptoms were categorized as unexplained END (ux-END). The PVS-Alberta Stroke Program Early CT Score (ASPECTS) score was used to evaluate the asymmetric cerebral venous signal on the susceptibility-weighted imaging sequences semiquantitatively. RESULTS: A total of 116 eligible patients were included, 18 (15.5%) of whom presented with ux-END. The 72 hour National Institutes of Health Stroke Scale was strongly correlated with diffusion-weighted imaging infarct volume and PVS-ASPECTS and was significantly higher in the ux-END group (16 ± 6 vs. 5 ± 4, P = 0.001). The PVS-ASPECTS score was significantly associated with poor outcomes (odds ratio 2.551, 95% confidence interval (CI) 1.722-3.780, P＜0.001), and PVS-ASPECTS (area under the curve 0.884, 95% CI 0.815-0.953, P < 0.001) was superior to diffusion-weighted imaging infarct volume (area under the cure 0.720, 95% CI 0.620-0.820, P = 0.001) in predicting 3-month poor outcome. At the optimal cut-off of 2, the PVS-ASPECT predicted poor outcomes with a sensitivity of 89.7% and a specificity of 78.2%. CONCLUSIONS: PVS 72 hours after EVT correlated with ux-END. The PVS-ASPECTS is a more reliable predictor of stroke prognosis and provides valuable information regarding post-EVT management.

A Rare B-Myeloid Conversion of Follicular Lymphoma into Clonally Related Acute Myeloid Leukemia: A Case Report.

Follicular lymphoma (FL) is a highly prevalent indolent lymphoma, and the risk of histological transformation is approximately 2-3% per year. Transformation of FL generally occurs in the same lineage (B cell lineage). Another rare form of disease progression is the transformation of neoplastic B-cells to another cell lineage such as acute myeloid leukemia (AML). The low incidence of B-myeloid transformation associated with poor prognosis hinders the establishment of model systems to identify molecular mechanisms. A 64-year-old woman was diagnosed with FL and achieved a satisfactory response after six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Approximately one month after treatment terminated, the disease progressed to AML with an increased white blood cell count and abnormal coagulation. Interestingly, nucleotide sequence analysis of the genomic region encoding the immunoglobulin heavy-chain variable domain showed the possibility of homologous transformation from lymphoma to leukemia cells. Although the patient experienced transient improvement after undergoing treatment with one cycle of idarubicin and cytarabine combined with etoposide, she relapsed and died 8 days after venetoclax salvage therapy. Patient with B-myeloid transformation was associated with an aggressive clinical course and poor prognosis. Conventional strategies for treating histologically transformed AML were ineffective. However, treatment with a Bcl-2 inhibitor could serve as an option. Here we review the literature relevant to this rare histological transformation of FL.

A Non-Linear Role of Hyperlipidemia on Progression of Intracranial Atherosclerotic Plaques and Acute Downstream Ischemic Events.

AIM: Intracranial atherosclerotic stenosis (ICAS) is the leading cause of ischemic stroke worldwide. Hyperlipidemia is a major contributor to atherosclerosis. However, the effect of hyperlipidemia on the evolution of intracranial atherosclerotic plaques and downstream ischemic episodes remains unclear. In this study, we aimed to assess the radiological features of ICAS plaques and to explore the relationship between hyperlipidemia and plaque progression. METHODS: We included people with ICAS (≥50% stenosis) undergoing high-resolution magnetic resonance imaging. The culprit plaque was defined as the sole, or in case of multiple stenosis, the narrowest plaque on the intracranial artery responsible for acute ischemic stroke. Demographic, clinical data, plaque features on MRI, and lipid parameters were compared between culprit and non-culprit plaques. Plaque enhancement was graded as Grade 0, 1 and 2 by comparing to the adjacent normal vessel wall and pituitary funnel after contrast enhancement on T1-weighted sequences. RESULTS: 162 patients were included (mean age 57.7±12.1 years, male 61.6%), 110 of whom were identified as culprit plaque with an ipsilateral acute stroke. High-grade enhancement was the most prominent MRI feature of the culpable plaque (Grade-2: OR 6.539, 95%CI 1.706-23.707, p=0.006). LDL cholesterol was significantly associated with overall acute ischemic stroke caused by culprit plaque. After stratification by enhancement grading LDL was independently associated with ischemic events in Grade-1 enhancement plaques (OR 6.778, 95%CI 2.122-21.649, p=0.001). In patients with Grade-2 enhancement plaques, however, LDL was not associated with ischemic event; in contrast, Neutrophil/Lymphocyte ratio was independently associated with ischemic events caused by Grade-2 enhancement plaques (OR 2.188, 95%CI 1.209-3.961, p=0.010). CONCLUSIONS: LDL was related with ischemia events in intermediate stage of intracranial atherosclerotic plaque progression, an excellent period for intensive lipid-lowering treatment. In advanced stage, inflammatory agents maybe the main contributor to ischemic events.

Plant life history strategies vary in subtropical forests with different disturbance histories: an assessment of biodiversity, biomass, and functional traits.

Disturbance alters environmental conditions in forests. Plants growing in forests with different disturbance histories in diverse environments may adopt varying life history strategies, but few studies focus on this effect. This study comprehensively investigated plant biodiversity, biomass, and functional traits in subtropical forests with two different disturbance histories in east China to explore differences in life history strategies. Biodiversity was slightly higher in disturbed compared to conserved forests. Significantly higher biomass was measured in conserved relative to disturbed evergreen broadleaved forests (P < 0.05). In conserved forests, leaf tissue density (LTD) was significantly higher and leaf thickness (LT), leaf dry matter content (LDMC), twig tissue density (TTD), twig dry matter content (TDMC), bark tissue density (BTD) and dry matter content (BDMC), and stem tissue density (STD) and dry matter content (SDMC) were significantly lower than in disturbed forests (P < 0.05). In terms of associated plant biodiversity, biomass, and functional traits, conserved forests adopted a resource acquisition strategy, reducing biodiversity and developing multiple functional traits such as high leaf area and specific leaf area and low LT, LDMC, TTD, TDMC, BTD, BDMC, STD, and SDMC to support a high biomass accumulation rate. Disturbed forests adopted a resource conservation strategy, enhancing biodiversity and developing converse trait combinations to lower the rate of biomass accumulation. A comprehensive investigation of plant biodiversity, biomass, and functional traits and subsequent assessment of plant life history strategies in conserved and disturbed forests will aid investigations of regional biodiversity and carbon reserves, contribute data to the TRY and Chinese plant trait databases, and improve ecological management and restoration efforts in east China.

A Qualitative Signature to Identify TERT Promoter Mutant High-Risk Tumors in Low-Grade Gliomas.

Background: Telomerase reverse transcriptase promoter (TERT-p) mutation has been frequently found, but associated with contrary prognosis, in both low-grade gliomas and glioblastomas. For the low-grade gliomas (Grades II-III), TERT-p mutant patients have a better prognosis than the wildtype patients, whereas for the GBMs (Grade IV), TERT-p mutation is related to a poor prognosis. We hypothesize that there exist high-risk patients in LGGs who share GBM-like molecular features, including TERT-p mutation, and need more intensive treatment than other LGGs. A molecular signature is needed to identify these high-risk patients for an accurate and timely treatment. Methods: Using the within-sample relative expression orderings of gene pairs, we identified the gene pairs with significantly stable REOs, respectively, in both the TERT-p mutant LGGs and GBMs but with opposite directions in the two groups. These reversely stable gene pairs were used as the molecular signature to stratify the LGGs into high-risk and low-risk groups. Results: A signature consisting of 21 gene pairs was developed, which can classify LGGs into two groups with significantly different overall survival. The high-risk group has a similar genetic mutation profile and a similar survival profile as GBMs, and these high-risk tumors may progress to a more malignant state. Conclusion: The 21 gene-pair signature based on REOs is capable of identifying high-risk patients in LGGs and guiding the clinical choice for appropriate and timely intervention.

Humic Substances Derived From Biomass Waste During Aerobic Composting and Hydrothermal Treatment: A Review.

Humic substances (HSs) occupy 80% of organic matter in soil and have been widely applied for soil remediation agents, potential battery materials, and adsorbents. Since the HS extraction rate is very low by microbial degradation in nature, artificial humification processes such as aerobic composting (AC) and hydrothermal treatment (HT) have attracted a great deal of attention as the most important strategies in HS production. This article aims to provide a state-of-the-art review on the development of conversion of biomass waste into HSs based on AC and HT for the first time in terms of mechanisms, characteristics of HSs' molecular structure, and influencing factors. In addition, some differences based on the aforementioned information between AC and HT are reviewed and discussed in the conversion of biomass waste into HSs in a pioneering way. For biomass waste conversion, a feasible strategy on effective humification processes by combining AC with HT is proposed.

Effects of Early-Stage Blood Pressure Variability on the Functional Outcome in Acute Ischemic Stroke Patients With Symptomatic Intracranial Artery Stenosis or Occlusion Receiving Intravenous Thrombolysis.

Background: Studies exploring the relationship between blood pressure (BP) fluctuations and outcome in acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) are limited. We aimed to investigate the influence of blood pressure variability (BPV) during the first 24 h after IVT on early neurological deterioration (END) and 3-month outcome after IVT in terms of different stroke subtypes. Methods: Clinical data from consecutive AIS patients who received IVT were retrospectively analyzed. The hourly systolic BP of all patients were recorded during the first 24 h following IVT. We calculated three systolic BPV parameters, including coefficient of variability (CV), standard deviation of mean BP (SD) and successive variation (SV), within the first 6, 12, and 24 h after IVT. END was defined as neurological deterioration with an increase in the National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 points within the first 72 h after admission. Follow-up was performed at 90 days after onset, and favorable and poor outcomes were defined as a modified Rankin Scale scores (mRS) of ≤1 or ≥2, respectively. Results: A total of 339 patients, which were divided into those with (intracranial artery stenosis or occlusion group, SIASO group) and without (non-SIASO group) SIASO, were included. Among them, 110 patients (32.4%) were with SIASO. Patients in SIASO group had higher NIHSS on admission and difference in term of mRS at 90 days compared with non-SIASO group (P < 0.001). In SIASO group, patients in favorable outcome group were younger and had lower NIHSS on admission, lower SV-24 h (14.5 ± 4.3 vs. 11.8 ± 3.2, respectively) and lower SD-24 h (12.7 ± 3.8 vs. 10.9 ± 3.3, respectively), compared with patients with poor outcome (all P < 0.05). In the multivariable logistic regression analysis, compared with the lowest SV (SV < 25% quartile), SV50-75% [odds ratio (OR) = 4.449, 95% confidence interval (CI) = 1.231-16.075, P = 0.023] and SV>75% (OR = 8.676, 95% CI = 1.892-39.775, P = 0.005) were significantly associated with poor outcome at 3 months in patients with SIASO, adjusted for age, NIHSS on admission and atrial fibrillation. No BPV parameters were associated with END in SIASO group. In non-SIASO group, there were no significant association between BPV patterns and END or 90-day outcome. Conclusions: SV-24 h had a negative relationship with 3-month outcome in AIS patients with SIASO treated with IVT, indicating that BPV may affect the outcome of AIS.

The complete mitochondrial genome of Hylarana latouchii (Anura: Ranidae) and its phylogenetic analysis.

We reported the complete mitochondrial genome (mitogenome) of broad-folded frog (Hylarana latouchii). This mitogenome is 17,007 bp in size and consists of 13 protein-coding genes, 22 transfer RNAs, two ribosomal RNAs, and one non-coding sequence (D-loop). The total composition was 58.54% A + T and 41.46% G + C (T: 29.31%, C: 27.33%, A: 29.23%, and G: 14.13%). The phylogenetic analysis revealed that H. latouchii formed a clade with other two species of genus Hylarana. This mitogenomic sequence of H. latouchii provides useful data to study its population genetics and phylogeography.

Wireless Power Transmission for Implantable Medical Devices Using Focused Ultrasound and a Miniaturized 1-3 Piezoelectric Composite Receiving Transducer.

Wireless power transmission (WPT) using ultrasound is a promising way for wirelessly recharging implantable medical devices (IMDs). However, the transmitted power using ultrasound so far is insufficient for driving the existing IMDs. Moreover, the size of the receiving transducer is larger, which is not suitable for implantation. To increase the output power and reduce the size of the implantable receiver, this article presents a method of combining focused ultrasound with a miniaturized 1-3 piezoelectric composite receiving transducer to produce higher electrical power. An analytical fluid-structure interaction model is constructed to fully understand the operating mechanism of the receiving transducer under ultrasonic force. In our experiments, a miniaturized 1-3 piezoelectric composite receiving transducer with a diameter of 3.7 mm was used. The output power generated from the receiving transducer reached 60 mW at a distance of 150 mm. In vitro and in vivo animal experiments proved that the miniaturized transducer could successfully receive focused ultrasonic energy and convert it to electrical power. The method presented and the electrical power that we obtained can provide a valuable reference for wirelessly charging of IMDs.

Promising Response to Lenalidomide-Combination Therapy in a Discordant Lymphoma Consisting of EBV-Positive Diffuse Large B-Cell Lymphoma and Angioimmunoblastic T-Cell Lymphoma: A Case Report.

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) complicated with angioimmunoblastic T-cell lymphoma (AITL) is extremely rare and typically shows an aggressive clinical course and unsatisfactory prognosis. Here, we describe the case of a 77-year-old man who was referred to the hospital because of repeated fever, night sweats, and weight loss. He was finally diagnosed with a discordant lymphoma consisting of AITL and DLBCL, with significantly different maximum standardized uptake values on positron emission tomography/computed tomography. Based on his complex illness and poor performance status, the patient received six cycles of lenalidomide combined with R-miniCHOP regimen and achieved complete remission with tolerable and controlled toxicity. He subsequently received lenalidomide maintenance therapy and achieved sustained remission. We consider the possible causes of this discordance involved AITL and EBV-positive DLBCL, and the possible mechanism of lenalidomide action in both T-cell and B-cell non-Hodgkin lymphomas. Lenalidomide-combination therapy may be a preferable choice in patients with an EBV-associated discordant lymphoma.

Successful PD-1 inhibitor treatment in a patient with refractory transformed follicular lymphoma who failed to respond to CAR-T cell therapy: a case report and literature review.

Follicular lymphoma (FL) accounts for approximately 35% of all non-Hodgkin lymphomas and can progress to diffuse large B cell lymphoma (DLBCL) at a rate of 2% per year. Here, we present a 56-year-old female patient who was diagnosed with grade 3a FL. Further pathological investigation revealed that the lymphoma had transformed into DLBCL following six courses of R-CHOP regimen, and further disease progression was observed after two courses of R2-GemOx. We ultimately failed to collect hematopoietic stem cells after two courses of R2-ICE. CD-22 CAR-T cell therapy salvaged the patient; however, a new soft tissue mass of 4.8 × 4.1 cm rapidly emerged in the patient's right lung. Following the observation of strong tissue staining of PD-L1 (90%), the patient was administered PD-1 inhibitor and 26 Gy of radiotherapy and has maintained progression-free survival at more than 15 months of follow-up. Transformed FL with strong PD-L1 expression showed a poor response to standard immunochemotherapy. Our findings support the potential benefit of PD-1 inhibitor and combination therapies in this type of transformed FL.

Characterization of the complete mitochondrial genome of the Chong'an Moustache Toad, Leptobrachium liui (Pope, 1947) with a phylogenetic analysis of Megophryidae.

The Chong'an Mustache Toad, Leptobrachium liui (Pope, 1947) is a Chinese endemic species, inhabiting the mountain streams with rich vegetation in southeastern China. The first complete mitochondrial genome (mitogenome) of L. liui was assembled using the data of whole-genome sequencing. The size of the complete mitogenome for L. liui was 17,190 bp, which included 13 PCGs, 23 tRNAs with two concatenated tRNAMet genes, 2 rRNAs, a non-coding region, and a D-loop. The Bayesian tree shows that L. liui was positioned near L. leishanense within the genus Leptobrachium.

Next-generation sequencing yields the complete mitochondrial genome of Microhyla beilunensis (Anura: Microhylidae).

The complete mitochondrial genome (mtDNA) of Microhyla beilunensis (Anura: Microhylidae) was sequenced and annotated. The length of mtDNA sequences of M. beilunensis was 16,721 bp, and encoded 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and a control region. The overall nucleotide composition of this genome was 29.1% A, 24.5% C, 14.5% G, 31.9% T, with a total A + T content of 61%. Phylogenetic analysis using Bayesian Inference (BI) method revealed that M. beilunensis was closely related with other 8 species from the genus Microhyla. The mtDNA dataset could be utilized for studying the molecular ecology and population genetics of Microhylid frogs.