bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of the accuracy of 11 different diagnostic tests for the detection of Schistosomiasis mansoni in individuals from a Brazilian area of low endemicity using latent class analysis
Authors: Mesquita Silvia Gonçalves , Caldeira Roberta Lima , Favre Tereza Cristina , Massara Cristiano Lara , Beck Lílian Christina Nóbrega Holsbach , Simões Taynãna César , de Carvalho Gardênia Braz Figueiredo , dos Santos Neves Flória Gabriela , de Oliveira Gabriela , de Souza Barbosa Lacerda Larisse , de Almeida Matheus Alves , dos Santos Carvalho Omar , Moraes Mourão Marina , Oliveira Edward , Silva-Pereira Rosiane A. , Fonseca Cristina Toscano
Published: December 2022

Background

Schistosomiasis is a parasitic disease associated with poverty. It is estimated that 7.1 million people are infected with Schistosoma mansoni in Latin America, with 95% of them living in Brazil. Accurate diagnosis and timely treatment are important measures to control and eliminate schistosomiasis, but diagnostic improvements are needed to detect infections, especially in areas of low endemicity.

Methodology

This research aimed to evaluate the performance of 11 diagnostic tests using latent class analysis (LCA). A cross-sectional survey was undertaken in a low endemicity area of the municipality of Malacacheta, Minas Gerais, Brazil. Feces, urine, and blood samples were collected from 400 residents older than 6 years of age, who had not been treated with praziquantel in the 12 months previous to the collection of their samples. The collected samples were examined using parasitological (Helm Test® kit Kato-Katz), nucleic acid amplification tests -NAATs (PCR, qPCR and LAMP on urine; PCR-ELISA, qPCR and LAMP on stool), and immunological (POC-CCA, the commercial anti-Schistosoma mansoni IgG ELISA kit from Euroimmun, and two in-house ELISA assays using either the recombinant antigen PPE or the synthetic peptide Smp150390.1) tests.

Results

The positivity rate of the 11 tests evaluated ranged from 5% (qPCR on urine) to 40.8% (commercial ELISA kit). The estimated prevalence of schistosomiasis was 12% (95% CI: 9–15%) according to the LCA. Among all tests assessed, the commercial ELISA kit had the highest estimated sensitivity (100%), while the Kato-Katz had the highest estimated specificity (99%). Based on the accuracy measures observed, we proposed three 2-step diagnostic approaches for the active search of infected people in endemic settings. The approaches proposed consist of combinations of commercial ELISA kit and NAATs tests performed on stool. All the approaches had higher sensitivity and specificity than the mean values observed for the 11 tests (70.4 and 89.5%, respectively).

Conclusion

We showed that it is possible to achieve high specificity and sensitivity rates with lower costs by combining serological and NAATs tests, which would assist in the decision-making process for appropriate allocation of public funding aiming to achieve the WHO target of eliminating schistosomiasis as a public health problem by 2030.
Simultaneous overexpression of ∆6-, ∆12- and ∆9-desaturases enhanced the production of γ-linolenic acid in Mucor circinelloides WJ11
Authors: Wang Xiuwen , Yang Junhuan , Mohamed Hassan , Shah Aabid Manzoor , Li Shaoqi , Pang Shuxian , Wu Chen , Xue Futing , Shi Wenyue , Sadaqat Beenish , Song Yuanda
Published: December 2022

Mucor circinelloides WJ11, an oleaginous filamentous fungus, produces 36% lipid of its cell dry weight when cultured in a high C/N ratio medium, however, the yield of γ-linolenic acid (GLA) is insufficient to make it competitive with other plant sources. To increase the GLA content in M. circinelloides WJ11, this fungus was engineered by overexpression of its key genes such as Δ6-, Δ12-, and Δ9-desaturases involved in GLA production. Firstly, we tried to overexpress two Δ6-desaturase isozymes to determine which one played important role in GLA synthesis. Secondly, Δ6-and Δ12-desaturase were co-overexpressed to check whether linoleic acid (LA), the precursor for GLA synthesis, is a limiting factor or not. Moreover, we tried to explore the effects of simultaneous overexpression of Δ6-, Δ12-, and Δ9-desaturases on GLA production. Our results showed that overexpression (1 gene) of DES61 promoted higher GLA content (21% of total fatty acids) while co-overexpressing (2 genes) DES61 and DES12 and simultaneous overexpressing (3 genes) DES61, DES12, and DES91 increased the GLA production of engineered strains by 1.5 folds and 1.9 folds compared to the control strain, respectively. This study provided more insights into GLA biosynthesis in oleaginous fungi and laid a foundation for further increase in GLA production into fungus such as M. circinelloides.
Identification of a small molecule 0390 as a potent antimicrobial agent to combat antibiotic-resistant Escherichia coli
Authors: Li Linhui , She Pengfei , Liu Shasha , Li Yimin , Li Zehao , Yang Yifan , Zhou Linying , Wu Yong
Published: December 2022

Introduction

Antibiotic resistance has posed a serious challenge to global public health. With the increasing resistance emergence of E. coli and mortality caused by drug-resistant E. coli infections, it is urgent to develop novel antibiotics.

Methods

By high-throughput screening assay, we found a bioactive molecule, 0390 (6056–0390), which demonstrated antimicrobial effects against E. coli. The antimicrobial effects of 0390 alone or in combination with conventional antibiotics were assessed by scanning electron microscopy, transmission electron microscopy, drug combination assay, and growth inhibition assay. In addition, we investigated the antimicrobial efficacy in subcutaneous infection model in vivo

Results

0390 showed significant synergistic antimicrobial effects in combination with SPR741, a polymyxin B derivative, against E. coli standard strain and extensively drug-resistant (XDR) clinical isolates, and the combination exhibited good safety property in vitro. In addition, we demonstrated that the combinational treatment of 0390 and SPR741 exhibited a considerable antibacterial activity in vivo, and no tissue damage or other toxicity was observed after the therapeutic dose treatment.

Discussion

To confront the issue of the infectious diseases related to E. coli and its multidrug resistant strains, potential approaches, such as new antibacterial agents with different structures from conventional antibiotics and drug combinations, are urgently needed. In this study, we have determined the in vitro and in vivo antimicrobial potential of 0390 alone or in combination with SPR741, which might be used as a treatment option for E. coli related infections.
The role of bile acid metabolism in the occurrence and development of NAFLD
Authors: Bing Hao , Li Yi-Ling
Published: December 2022

Non-alcoholic fatty liver disease (NAFLD) has become one of the important causes of cirrhosis and liver cancer, resulting in a huge medical burden worldwide. Currently, effective non-invasive diagnostic indicators and drugs for NAFLD are still lacking. With the development of metabolomics technology, the changes in metabolites during the development of NAFLD have been gradually revealed. Bile acid (BA) is the main endpoint of cholesterol metabolism in the body. In addition, it also acts as a signaling factor to regulate metabolism and inflammation in the body through the farnesyl X receptor and G protein-coupled BA receptor. Studies have shown that BA metabolism is associated with the development of NAFLD, but a large number of animal and clinical studies are still needed. BA homeostasis is maintained through multiple negative feedback loops and the enterohepatic circulation of BA. Recently, treatment of NAFLD by interfering with BA synthesis and metabolism has become a new research direction. Here, we review the changes in BA metabolism and its regulatory mechanisms during the development of NAFLD and describe the potential of studies exploring novel non-invasive diagnostic indicators and therapeutic targets for NAFLD based on BA metabolism.
PDX1 is the cornerstone of pancreatic β-cell functions and identity
Authors: Ebrahim Nour , Shakirova Ksenia , Dashinimaev Erdem
Published: December 2022

Diabetes has been a worldwide healthcare problem for many years. Current methods of treating diabetes are still largely directed at symptoms, aiming to control the manifestations of the pathology. This creates an overall need to find alternative measures that can impact on the causes of the disease, reverse diabetes, or make it more manageable. Understanding the role of key players in the pathogenesis of diabetes and the related β-cell functions is of great importance in combating diabetes. PDX1 is a master regulator in pancreas organogenesis, the maturation and identity preservation of β-cells, and of their role in normal insulin function. Mutations in the PDX1 gene are correlated with many pancreatic dysfunctions, including pancreatic agenesis (homozygous mutation) and MODY4 (heterozygous mutation), while in other types of diabetes, PDX1 expression is reduced. Therefore, alternative approaches to treat diabetes largely depend on knowledge of PDX1 regulation, its interaction with other transcription factors, and its role in obtaining β-cells through differentiation and transdifferentiation protocols. In this article, we review the basic functions of PDX1 and its regulation by genetic and epigenetic factors. Lastly, we summarize different variations of the differentiation protocols used to obtain β-cells from alternative cell sources, using PDX1 alone or in combination with various transcription factors and modified culture conditions. This review shows the unique position of PDX1 as a potential target in the genetic and cellular treatment of diabetes.
Prognostic value, immune signature and molecular mechanisms of the SUMO family in pancreatic adenocarcinoma
Authors: Duan Yunjie , Du Yongxing , Mu Yongrun , Gu Zongting , Wang Chengfeng
Published: December 2022

Background: Pancreatic adenocarcinoma (PAAD) has a high degree of malignancy and a very poor prognosis, and the 5-year overall survival rate of patients is approximately 7%. To improve the prognosis of patients with PAAD, a more comprehensive and in-depth study of the pathogenesis of PAAD and the identification of new diagnostic markers and treatment targets are urgently needed. Increasing evidence supports that the small ubiquitin-like modifier (SUMO) family is closely related to the occurrence and development of a variety of cancers. However, the function of the SUMO family in PAAD is not clear, and related research is very scarce.

Methods: R, Cytoscape, cBioPortal, and other software and online databases were used to comprehensively analyze the expression characteristics, prognostic value, and oncogenic mechanism of the SUMO family in PAAD.

Results: SUMO family members are highly expressed in PAAD, and high expression of SUMO family members is significantly associated with poor clinicopathological features and poor prognosis in PAAD patients. In addition, SUMO family members are significantly coexpressed with M6A methylation regulators and various oncogenes and play an activating role in various oncogenic pathways, including EMT. Furthermore, it is worth noting that the close association between SUMO family members and TP53 mutation status and the negative regulatory effect of SUMO1/2 on PAAD immunity may represent the potential mechanism by which SUMO family members promote the development of PAAD. Moreover, the coexpression characteristics of SUMO family members and a variety of cancer-promoting immune checkpoint genes, as well as the positive correlation between SUMO4 expression level and the sensitivity of various targeted or chemotherapeutic drugs, including gemcitabine, paclitaxel, and doxorubicin, suggest future clinical directions of this study.

Conclusion: The SUMO family is closely related to the occurrence and development of PAAD and can be used as a new biomarker and therapeutic target for patients with PAAD.
Potential roles of oxidative distress on neurodegeneration in Parkinson's disease with neuropsychiatric symptoms
Authors: Li Dan-ning , Lian Teng-hong , Zhang Wei-Jiao , Zhang Ya-nan , Guo Peng , Guan Hui-ying , Li Jing-hui , He Ming-yue , Zhang Wen-jing , Zhang Wei-jia , Luo Dong-mei , Wang Xiao-min , Zhang Wei
Published: December 2022

Background

Neuropsychiatric symptoms (NPSs) belong to a category of non-motor symptoms of Parkinson's disease (PD), which seriously compromise the quality of life and prognosis of PD. This study focused on the correlations between NPSs, free radicals, neuroinflammatory factors, and neuropathological proteins in cerebrospinal fluid (CSF) in patients with PD, aiming to provide insights into the potential mechanisms and therapeutic target for PD with NPSs (PD-NPSs).

Methods

In total, 129 patients with PD were enrolled and assessed by the Neuropsychiatric Symptoms Inventory (NPI); they were divided into the PD-NPSs group (75 patients) and PD with no NPSs (PD-nNPSs) group (54 patients). The levels of hydrogen peroxide (H2O2) and nitric oxide (NO), and hydroxyl radical (·OH), anti-oxidative enzyme, neuroinflammatory factors, and neuropathological proteins in CSF from patients with PD were measured. The levels of the above variables were compared between PD-NPSs and PD-nNPSs groups, and correlation analyses among the above variables were conducted.

Results

(1) The levels of H2O2 and NO in CSF from the PD-NPSs group were significantly elevated compared with the PD-nNPSs group (p = 0.001), and NPI score positively correlated with the levels of H2O2 and NO (r = 0.283, P = 0.001; r = 0.231, P = 0.008). Reversely, total superoxide dismutase (tSOD) activity in CSF from the PD-NPSs group was significantly reduced compared with the PD-nNPSs group (p = 0.011), and negatively correlated with NPI score (r = −0.185, p = 0.036). (2) The tumor necrosis factor (TNF)-α level in CSF from the PD-NPSs group was significantly decreased compared with the PD-nNPSs group (p = 0.002) and negatively correlated with NPI score (r = −0.211, p = 0.016). (3) The total tau (T-tau) level in CSF from the PD-NPSs group was significantly higher than in the PD-nNPSs group (p = 0.014) and positively correlated with the NPI score (r = 0.167, p = 0.060). (4) The levels of H2O2 and NO positively correlated with the T-tau level in CSF from the PD-NPSs group (r = 0.183, p = 0.039; r = 0.251, P = 0.004), and the levels of TNF-α and T-tau showed a negative correlation (r = −0.163, p = 0.067).

Conclusion

Oxidative distress characterized by the elevations of H2O2 and NO levels may closely correlate with the neurodegeneration in brain regions related to PD-NPSs. Thus, therapeutic antioxidants may become an important target for PD-NPSs therapy.
A lightweight multi-dimension dynamic convolutional network for real-time semantic segmentation
Authors: Zhang Chunyu , Xu Fang , Wu Chengdong , Xu Chenglong
Published: December 2022

Semantic segmentation can address the perceived needs of autonomous driving and micro-robots and is one of the challenging tasks in computer vision. From the application point of view, the difficulty faced by semantic segmentation is how to satisfy inference speed, network parameters, and segmentation accuracy at the same time. This paper proposes a lightweight multi-dimensional dynamic convolutional network (LMDCNet) for real-time semantic segmentation to address this problem. At the core of our architecture is Multidimensional Dynamic Convolution (MDy-Conv), which uses an attention mechanism and factorial convolution to remain efficient while maintaining remarkable accuracy. Specifically, LMDCNet belongs to an asymmetric network architecture. Therefore, we design an encoder module containing MDy-Conv convolution: MS-DAB. The success of this module is attributed to the use of MDy-Conv convolution, which increases the utilization of local and contextual information of features. Furthermore, we design a decoder module containing a feature pyramid and attention: SC-FP, which performs a multi-scale fusion of features accompanied by feature selection. On the Cityscapes and CamVid datasets, LMDCNet achieves accuracies of 73.8 mIoU and 69.6 mIoU at 71.2 FPS and 92.4 FPS, respectively, without pre-training or post-processing. Our designed LMDCNet is trained and inferred only on one 1080Ti GPU. Our experiments show that LMDCNet achieves a good balance between segmentation accuracy and network parameters with only 1.05 M.
Decompressive craniectomy: Comparative analysis between surgical time and better prognosis
Authors: Bem Junior Luiz Severo , Silva Ana Cristina Veiga , Menezes Marcelo Diniz de , Galvão Maria Júlia Tabosa de Carvalho , Ferreira Neto Otávio da Cunha , Alencar Neto Joaquim Fechine de , Rabelo Nicollas Nunes , Almeida Nivaldo Sena , Valença Marcelo Moraes , Azevedo Filho Hildo Rocha Cirne de
Published: December 2022

Background

Malignant ischemic stroke is characterized by the involvement of 2/3 of the area of the middle cerebral artery, associated with cerebral edema, intracranial hypertension (ICH) and cerebral herniation, generating high morbidity and mortality. Over the years, several therapies have been studied in an attempt to reverse or reduce the damage caused by this vascular disorder, including decompressive craniectomy (DC), a surgical technique reserved for cases that evolve with refractory ICH.

Methods

This study seeks to perform a comparative analysis on the effectiveness of decompressive craniectomy using four randomized clinical trials and the results found in the retrospective study conducted in a neurosurgical reference center between 2010 and 2018.

Results

The total sample consisted of 263 patients, among which 118 were randomized and 145 were part of the retrospective study. The outcome was analyzed based on the modified Rankin Scale (mRS) for 6 and 12 months. The mean time to perform the DC was 28.4 h in the randomized trials, with the late approach (> 24 h) associated with unfavorable outcomes (mRS between 4 and 6).

Conclusion

Compared to the aforementioned studies, the study by Bem Junior et al. shows that a surgical approach in < 12 h had a better outcome, with 70% of the patients treated early classified as mRS 2 and 3 at the end of 12 months (1). Decompressive craniectomy is currently the most effective measure to control refractory ICH in cases of malignant ischemic stroke, and the most appropriate approach before surgery is essential for a better prognosis for patients.
Rostro-caudal networks for sound processing in the primate brain
Authors: Scott Sophie K. , Jasmin Kyle
Published: December 2022

Sound is processed in primate brains along anatomically and functionally distinct streams: this pattern can be seen in both human and non-human primates. We have previously proposed a general auditory processing framework in which these different perceptual profiles are associated with different computational characteristics. In this paper we consider how recent work supports our framework.
Bi-objective goal programming for balancing costs vs. nutritional adequacy
Authors: Koenen Melissa F. , Balvert Marleen , Fleuren Hein
Published: December 2022

Introduction

Linear programming (LP) is often used within diet optimization to find, from a set of available food commodities, the most affordable diet that meets the nutritional requirements of an individual or (sub)population. It is, however, not always possible to create a feasible diet, as certain nutritional requirements are difficult to meet. In that case, goal programming (GP) can be used to minimize deviations from the nutritional requirements in order to obtain a near feasible diet. With GP the cost of the diet is often overlooked or taken into account using the ε-constraint method. This method does not guarantee to find all possible trade-offs between costs and nutritional deficiency without solving many uninformative LPs.

Methods

We present a method to find all trade-offs between any two linear objectives in a dietary LP context that is simple, does not solve uninformative LPs and does not need prior input from the decision maker (DM). This method is a bi-objective algorithm based on the NonInferior Set Estimation (NISE) method that finds all efficient trade-offs between two linear objectives.

Results

In order to show what type of insights can be gained from this approach, two analyses are presented that investigate the relation between cost and nutritional adequacy. In the first analysis a diet with a restriction on the exact energy intake is considered where all nutrient intakes except energy are allowed to deviate from their prescription. This analysis is especially helpful in case of a restrictive budget or when a nutritionally adequate diet is either unaffordable or unattainable. The second analysis only relaxes the exact energy intake, where the other nutrients are kept within their requirements, to investigate how the energy intake affects the cost of a diet. Here, we describe in what situations the so-called more-for-less paradox takes place, which can be induced by requiring an exact energy intake.

Conclusion

To the best of our knowledge, we are the first to address how to obtain all efficient trade-offs of two linear objectives in a dietary LP context and how this can be used for analyses.
Prognostic efficacy and prognostic factors of TACE plus TKI with ICIs for the treatment of unresectable hepatocellular carcinoma: A retrospective study
Authors: Han Ziqiang , Yang Faji , Zhang Ye , Wang Jianlu , Ni Qingqiang , Zhu Huaqiang , Zhou Xu , Gao Hengjun , Lu Jun
Published: December 2022

Hepatocellular carcinoma (HCC) remains a global challenge due to its high morbidity and mortality rates as well as poor response to treatment. Local combined systemic therapy is widely used in the treatment of unresectable hepatocellular cancer (uHCC). This retrospective study was to investigate the prognostic effect and prognostic factors of transcatheter arterial chemoembolization (TACE) plus tyrosine kinase inhibitors (TKI) with immune checkpoint inhibitors (ICIs) in the treatment of uHCC. A retrospective analysis of 171 patients with uHCC was performed in our hospital from April 27, 2015 to October 18, 2021. According to different treatment options, patients were divided into TACE group (n=45), TACE+TKI group (n=76) and TACE+TKI+ICIs group (n=50). In this study, we found that, the median overall survival (mOS) of TACE+TKI+ICIs group was significantly better than TACE+TKI group and TACE group [24.1 (95% CI 15.1-33.1) months vs 14.9 (95% CI 10.7-19.1) months vs 11.4 (95% CI 8.4-14.5) months, hazard ratio (HR) 0.62; 95% CI 0.47-0.81; P=0.002]. A visible difference in the median progression-free survival (mPFS) interval between the groups was discovered [10.6 (95% CI6.5-14.7) months in TACE+TKI+ICIs group vs. 6.7 (95% CI 5.5-7.9) months in the TACE+TKI group vs. 6 (95% CI 2.3-9.7) months in the TACE group (HR 0.66; 95% CI 0.53-0.83; P<0.001)]. The objective response rates (ORR) in the TACE group, TACE+TKI group, and TACE+TKI+ICIs group were 31.1%, 35.5%, and 42%, and the disease control rate (DCR) were 51.1%, 65.8%, and 80%. There were no adverse events (AEs) of arthralgia, diarrhea, rash, and pruritus in the TACE group. The incidence of grade 3 AEs (Hypertension) in the TACE+TKI+ICIs group was significantly higher than that in TACE+TKI and TACE groups (28% vs 17.1% vs 6.7%, P=0.024), and secondly, the morbidity of rash and pruritus in the TACE+TKI+ICIs group was apparently higher than that in the TACE+TKI group (P<0.05). Multivariate analysis showed that ECOG-PS 2 (HR=2.064, 95%CI 1.335-3.191, P=0.001), Hepatitis B virus (HR=2.539, 95%CI 1.291-4.993, P=0.007), AFP≥400 ng/ml (HR= 1.72, 95%CI 1.12-2.643, P=0.013), neutrophil-lymphocyte ratio (NLR) ≥2.195 (HR=1.669, 95%CI 1.073-2.597, P=0.023) were independent risk factors for OS in uHCC patients. So, TACE+TKI+ICIs therapy can prolong the OS and improve the prognosis of patients effectively, with a well-characterized safety profile.
Study protocol of an open-label prospective phase II umbrella study of precise neoadjuvant therapy for patients with stage II-IIIB resectable non-small cell lung cancer (PURPOSE)
Authors: Wang Yiyang , Zhai Haoran , Wang Jiaming , Mao Teng , Ji Chunyu , Bao Feichao , Gu Zhitao , Fang Wentao
Published: December 2022

Background

The outcomes of locally advanced non-small cell lung cancer (LA-NSCLC) are unfavorable mainly due to a high risk of cancer recurrence. Only around 5% of patients can benefit from perioperative chemotherapy which is the current standard treatment. Recently, promising results with neoadjuvant targeted and immune-therapy therapy have been seen. However, most clinical trials are looking for patients eligible for certain drugs, instead of seeking suitable treatments for certain patients. Therefore, it is necessary to look for more efficient perioperative therapies to increase resectability, reduce recurrence and improve prognosis.

Methods/Design

The study is an open-label, prospective, phase II, umbrella trial, enrolling patients diagnosed with treatment-naïve potentially resectable Stage II-IIIB NSCLC. Next-generation sequencing (NGS) using a 68-gene panel is performed for biopsies of tumor tissues from eligible patients. Enrolled patients are then stratified into six independent cohorts based on the status of gene mutations and PD-L1 status in tumor tissues, that is, ①EGFR 19del group, ②EGFR 21 L858R group, ③EGFR rare mutation group, ④Other driver mutation group, ⑤Drive mutation-negative group with PD-L1≥1%, ⑥Drive mutation-negative group with PD-L1<1%. A Simon’s two-stage design is performed in each cohort independently and patients receive corresponding standard therapies accordingly. We aim to enroll 26 patients in each cohort and totally 156 patients will be enrolled. The primary endpoint is objective response rate (ORR). Secondary endpoints include oncological prognosis and perioperative outcomes. Exploratory endpoint is to investigate patient-specific minimal residual disease (MRD) in predicting treatment efficacy and oncological prognosis.

Discussions

This is the first umbrella trial focusing on the safety and efficacy of precise neoadjuvant therapy for patients diagnosed with potentially resectable LA-NSCLC based on NGS results. The results of this trial would help improve overall treatment results in LA-NSCLC patients.

Trial registration

Chinese Clinical Trial Registry. Trial registration number: ChiCTR2100053021.

Advantages and limitations of this study

There is no neoadjuvant umbrella trial focusing on LA-NSCLCs. This is the first neoadjuvant umbrella trial, using a precise individualized approach and seeking suitable drugs for LA-NSCLC patients, with the aim to improve overall treatment outcomes.

Clinical trial registration

https://www.chictr.org.cn/, identifier ChiCTR2100053021.
Whole exome sequencing in Chinese mucinous pulmonary adenocarcinoma uncovers specific genetic variations different from lung adenocarcinoma
Authors: Zhang Chenyue , Wang Kai , Liu Wenjie , Lin Jiamao , Li Zhenxiang , Wang Hui , Zhao Chenglong , Chen Yanhua , Wu Shuangxiu , Yang Airong , Wu Jiayan , Wang Haiyong
Published: December 2022

Background

As a rare subtype of primary lung adenocarcinoma (LUAD), mucinous pulmonary adenocarcinoma (MPA) was considered a distinctive entity with unfavorable outcomes. Therefore, there is a great need for a better understanding of the genomic and immunological landscape of this rare tumor type, which would inform improved therapeutic strategies.

Methods

A total of 96 patients histologically confirmed with MPA were recruited from Shandong Cancer Hospital and Institute (SCH). Single nucleotide variation (SNV), copy number variation (CNV), genomic instability, and immunological landscape insights into 96 MPA patients were identified using WES.

Results

We demonstrated that MPAs had marked different genomic alterations and were more complex in genomic profiles than LUADs. Mutations in Tumor Protein 53 (TP53) and CYP7A Promoter-Binding Factor (CPF) pathways significantly shortened survival whereas mutations in Notch and Wnt pathways significantly prolonged survival in MPA. Besides, we demonstrated that mutations in immune-related genes influenced outcomes, with mutations in TP53, Ataxia Telangiectasia Mutated (ATM), Polymerase (DNA) Delta 1 (POLD1), and Epidermal Growth Factor Receptor (EGFR) correlated with worsened survival.

Conclusions

We not only depicted the genetic and immunologic landscape of Chinese MPA but also reveal its distinction from LUAD in genomic and immune context. Our findings may provide opportunities for therapeutic susceptibility among Chinese MPA patients.
Lipid droplets and ferroptosis as new players in brain cancer glioblastoma progression and therapeutic resistance
Authors: Bezawork-Geleta Ayenachew , Dimou James , Watt Matthew J.
Published: December 2022

A primary brain tumor glioblastoma is the most lethal of all cancers and remains an extremely challenging disease. Apparent oncogenic signaling in glioblastoma is genetically complex and raised at any stage of the disease’s progression. Many clinical trials have shown that anticancer drugs for any specific oncogene aberrantly expressed in glioblastoma show very limited activity. Recent discoveries have highlighted that alterations in tumor metabolism also contribute to disease progression and resistance to current therapeutics for glioblastoma, implicating an alternative avenue to improve outcomes in glioblastoma patients. The roles of glucose, glutamine and tryptophan metabolism in glioblastoma pathogenesis have previously been described. This article provides an overview of the metabolic network and regulatory changes associated with lipid droplets that suppress ferroptosis. Ferroptosis is a newly discovered type of nonapoptotic programmed cell death induced by excessive lipid peroxidation. Although few studies have focused on potential correlations between tumor progression and lipid droplet abundance, there has recently been increasing interest in identifying key players in lipid droplet biology that suppress ferroptosis and whether these dependencies can be effectively exploited in cancer treatment. This article discusses how lipid droplet metabolism, including lipid synthesis, storage, and use modulates ferroptosis sensitivity or tolerance in different cancer models, focusing on glioblastoma.
Hypoxia-responsive nanomaterials for tumor imaging and therapy
Authors: Xia Yifei , Duan Shao , Han Chaozhe , Jing Chengwei , Xiao Zunyu , Li Chao
Published: December 2022

Hypoxia is an important component of tumor microenvironment and plays a pivotal role in cancer progression. With the distinctive physiochemical properties and biological effects, various nanoparticles targeting hypoxia had raised great interest in cancer imaging, drug delivery, and gene therapy during the last decade. In the current review, we provided a comprehensive view on the latest progress of novel stimuli-responsive nanomaterials targeting hypoxia-tumor microenvironment (TME), and their applications in cancer diagnosis and therapy. Future prospect and challenges of nanomaterials are also discussed.
ASK120067 potently suppresses B-cell or T-cell malignancies in vitro and in vivo by inhibiting BTK and ITK
Authors: Song Peiran , Bai Gang , Chan Shingpan , Zhang Tao , Tong Linjiang , Su Yi , Shen Yanyan , Chen Yi , Liu Yingqiang , Lai Mengzhen , Ning Yi , Tang Haotian , Fang Yan , Chen Yi , Ding Ke , Ding Jian , Xie Hua
Published: December 2022

Hyperactivation of Bruton’s tyrosine kinase (BTK) or interleukin-2-inducible T cell kinase (ITK) has been attributed to the pathogenesis of B-cell lymphoma or T-cell leukemia, respectively, which suggests that Bruton’s tyrosine kinase and interleukin-2-inducible T cell kinase are critical targets for the treatment of hematological malignancies. We identified a novel third-generation epidermal growth factor receptor (EGFR) inhibitor, ASK120067 (limertinib) in our previous research, which has been applied as a new drug application against non-small cell lung cancer in China. In this work, we found that ASK120067 displayed potent in vitro inhibitory efficacy against Bruton’s tyrosine kinase protein and interleukin-2-inducible T cell kinase protein via covalent binding. In cell-based assays, ASK120067 dose-dependently suppressed Bruton’s tyrosine kinase phosphorylation and exhibited anti-proliferation potency by inducing apoptosis in numerous B-lymphoma cells. Meanwhile, it caused growth arrest and induced the apoptosis of T-cell leukemia cells by attenuating interleukin-2-inducible T cell kinase activation. Oral administration of ASK120067 led to significant tumor regression in B-cell lymphoma and T-cell leukemia xenograft models by weakening Bruton’s tyrosine kinase and interleukin-2-inducible T cell kinase signaling, respectively. Taken together, our studies demonstrated that ASK120067 exerted preclinical anti-tumor activities against B-/T-cell malignancy by targeting BTK/ITK.
Topological structure effects of Laguerre-Gaussian laser on self-collimation acceleration mechanism
Authors: Dong H. , Wang W. P. , Lv Z. X. , Jiang C. , He J. Z. , Leng Y. X. , Li R. X. , Xu Z. Z.
Published: December 2022

Energetic plasma beams can be generated through the interaction between a short-pulse high-intensity laser and solid target. However, obtaining collimated plasma beams with low divergence remains challenging. In this study, we devised a self-collimation scheme driven by a topologically structured Laguerre–Gaussian (LG) laser that irradiates a thin target in three-dimensional particle-in-cell simulations. It was observed that a high-density and narrow plasma beam could be formed by the intrinsic hollow intensity distribution of the LG laser. A magnetic tunnel was generated around the beam and collimated the plasma beam within a radius of hundreds of nanometers. This collimation can be enhanced by increasing the topological charge from l = 1 to l = 3 and then destroyed for a larger l. The collimation method is promising in applications requiring well-collimated energetic plasma beams, such as indirect drive inertial con-finement fusion, laboratory astrophysics, and radiation therapy.
Root system architecture and environmental flux analysis in mature crops using 3D root mesocosms
Authors: Dowd Tyler G. , Li Mao , Bagnall G. Cody , Johnston Andrea , Topp Christopher N.
Published: December 2022

Current methods of root sampling typically only obtain small or incomplete sections of root systems and do not capture their true complexity. To facilitate the visualization and analysis of full-sized plant root systems in 3-dimensions, we developed customized mesocosm growth containers. While highly scalable, the design presented here uses an internal volume of 45 ft3 (1.27 m3), suitable for large crop and bioenergy grass root systems to grow largely unconstrained. Furthermore, they allow for the excavation and preservation of 3-dimensional root system architecture (RSA), and facilitate the collection of time-resolved subterranean environmental data. Sensor arrays monitoring matric potential, temperature and CO2 levels are buried in a grid formation at various depths to assess environmental fluxes at regular intervals. Methods of 3D data visualization of fluxes were developed to allow for comparison with root system architectural traits. Following harvest, the recovered root system can be digitally reconstructed in 3D through photogrammetry, which is an inexpensive method requiring only an appropriate studio space and a digital camera. We developed a pipeline to extract features from the 3D point clouds, or from derived skeletons that include point cloud voxel number as a proxy for biomass, total root system length, volume, depth, convex hull volume and solidity as a function of depth. Ground-truthing these features with biomass measurements from manually dissected root systems showed a high correlation. We evaluated switchgrass, maize, and sorghum root systems to highlight the capability for species wide comparisons. We focused on two switchgrass ecotypes, upland (VS16) and lowland (WBC3), in identical environments to demonstrate widely different root system architectures that may be indicative of core differences in their rhizoeconomic foraging strategies. Finally, we imposed a strong physiological water stress and manipulated the growth medium to demonstrate whole root system plasticity in response to environmental stimuli. Hence, these new “3D Root Mesocosms” and accompanying computational analysis provides a new paradigm for study of mature crop systems and the environmental fluxes that shape them.
Comparative changes of health-promoting phytochemicals and sugar metabolism of two hardy kiwifruit (Actinidia arguta) cultivars during fruit development and maturity
Authors: Lin Yuanxiu , Tang Honglan , Zhao Bing , Lei Diya , Zhou Xuan , Yao Wantian , Fan Jinming , Zhang Yunting , Chen Qing , Wang Yan , Li Mengyao , He Wen , Luo Ya , Wang Xiaorong , Tang Haoru , Zhang Yong
Published: December 2022

Introduction

Hardy kiwifruit (Actinidia arguta) has an extensive range of nutritional and bioactive compounds and has been valued as a great resource for kiwifruit breeding. A better understanding of the dynamic changes of the composition and accumulation of nutritional compounds during fruit development and ripening is required before genetic or cultural improvements can be targeted.

Methods

In the present study, the phytochemical analysis of two A. arguta cultivars ‘Yilv’ and ‘Lvmi-1’ showed that they comprised different morphology, with a higher fruit diameter while a lower vertical fruit diameter of ‘Lvmi-1’ compared with ‘Yilv’. The antioxidant capacity of both cultivars decreased during the maturity time and showed no significant difference between them. Furthermore, although glucose gradually increased during the maturity time, the predominant sugar composition was speculated to be fructose in ‘Lvmi-1’ fruit while sucrose in ‘Yilv’ fruit at the early fruit developmental stages. Moreover, the predominant acids in ‘Yilv’ and ‘Lvmi-1’ were citric acid followed by quinic acid, malic acid, and oxalic acid. The expression of sugar- and starch-related genes encoding the crucial enzymes suggested different changes in ‘Yilv’ and ‘Lvmi-1’. Notably, a subsequent correlation analysis showed a significant positive correlation between sucrose phosphate synthase (SPS) expression and glucose in ‘Yilv’, fructokinase (FK) expression, and starch content in ‘Lvmi-1’, implying their vital roles in sugar and starch accumulation. By contrast, a significant negative correlation between FK expression and fructose in ‘Lvmi-1’ fruit was observed.

Results and Discussion

In summary, our results provide supplementary information for the dynamic changes of nutritional compounds and antioxidant capacity during hardy kiwifruit maturity time and give a clue for exploring the mechanism of sugar and starch accumulation in hardy kiwifruit.
Rhizospheric microbiomics integrated with plant transcriptomics provides insight into the Cd response mechanisms of the newly identified Cd accumulator Dahlia pinnata
Authors: Li Xiong , Li Boqun , Jin Tao , Chen Huafang , Zhao Gaojuan , Qin Xiangshi , Yang Yongping , Xu Jianchu
Published: December 2022

Phytoremediation that depends on excellent plant resources and effective enhancing measures is important for remediating heavy metal-contaminated soils. This study investigated the cadmium (Cd) tolerance and accumulation characteristics of Dahlia pinnata Cav. to evaluate its Cd phytoremediation potential. Testing in soils spiked with 5–45 mg kg–1 Cd showed that D. pinnata has a strong Cd tolerance capacity and appreciable shoot Cd bioconcentration factors (0.80–1.32) and translocation factors (0.81–1.59), indicating that D. pinnata can be defined as a Cd accumulator. In the rhizosphere, Cd stress (45 mg kg–1 Cd) did not change the soil physicochemical properties but influenced the bacterial community composition compared to control conditions. Notably, the increased abundance of the bacterial phylum Patescibacteria and the dominance of several Cd-tolerant plant growth–promoting rhizobacteria (e.g., Sphingomonas, Gemmatimonas, Bryobacter, Flavisolibacter, Nocardioides, and Bradyrhizobium) likely facilitated Cd tolerance and accumulation in D. pinnata. Comparative transcriptomic analysis showed that Cd significantly induced (P < 0.001) the expression of genes involved in lignin synthesis in D. pinnata roots and leaves, which are likely to fix Cd2+ to the cell wall and inhibit Cd entry into the cytoplasm. Moreover, Cd induced a sophisticated signal transduction network that initiated detoxification processes in roots as well as ethylene synthesis from methionine metabolism to regulate Cd responses in leaves. This study suggests that D. pinnata can be potentially used for phytoextraction and improves our understanding of Cd-response mechanisms in plants from rhizospheric and molecular perspectives.
A systematic assessment of how rootstock growth characteristics impact grafted tomato plant biomass, resource partitioning, yield, and fruit mineral composition
Authors: Gong Tian , Brecht Jeffrey K. , Koch Karen E. , Hutton Samuel F. , Zhao Xin
Published: December 2022

The appropriate selection of rootstock-scion combinations to improve yield and fully realize grafting benefits requires an in-depth understanding of rootstock-scion synergy. Toward this end, we grafted two determinate-type scions [grape tomato (‘BHN 1022') and beefsteak tomato (‘Skyway')] onto four rootstocks with different characteristics to examine plant growth, yield performance, biomass production, and fruit mineral nutrient composition. The study was conducted during two growing seasons (spring and fall plantings in Florida) under organic production in high tunnels with the non-grafted scions as controls. Rootstocks had previously been designated as either “generative” (‘Estamino') or “vegetative” (‘DR0141TX') by some commercial suppliers or had not been characterized [‘RST-04-106-T' and ‘SHIELD RZ F1 (61-802)']. Also, ‘Estamino', ‘DR0141TX', and ‘RST-04-106-T' had been described as more vigorous than ‘SHIELD RZ F1 (61-802)'. In both planting seasons (with low levels of soilborne disease pressure), the “vegetative” and “generative” rootstocks increased marketable and total fruit yields for both scions except for the beefsteak tomato grafted with the “vegetative” rootstock in fall planting. Positive effects of ‘RST-04-106-T' on fruit yield varied with scions and planting seasons, and were most manifested when grafted with the beefsteak tomato scion in fall planting. ‘SHIELD RZ F1 (61-802)' led to similar yields as the non-grafted controls except for grafting with the grape tomato scion in fall planting. For vegetative and fruit biomass, both the “vegetative” and “generative” rootstocks had positive impacts except for the beefsteak tomato in fall planting. For fruit mineral composition, the “vegetative” and “generative” rootstocks, both highly vigorous, consistently elevated fruit P, K, Ca, Zn, and Fe contents on a dry weight basis, whereas the other rootstocks did not. Overall, although the more vigorous rootstocks enhanced tomato plant productivity and fruit minerals, the evidence presented here does not support the suggestion that the so-called “vegetative” and “generative” rootstocks have different impacts on tomato scion yield, biomass production, or fruit mineral contents. More studies with different production systems and environmental conditions as well as contrasting scion genotypes are needed to further categorize the impacts of rootstocks with different vigor and other characteristics on plant biomass production and their implications on fruit yield development.
Possible northern persistence of Siebold’s beech, Fagus crenata, at its northernmost distribution limit on an island in Japan Sea: Okushiri Island, Hokkaido
Authors: Kitamura Keiko , Namikawa Kanji , Tsuda Yoshiaki , Kobayashi Makoto , Matsui Tetsuya
Published: December 2022

Siebold’s beech, Fagus crenata, is widely distributed across the Japanese Archipelago and islands in Japan Sea. Similar to the northern limit of the geographical distribution of F. crenata on the mainland of Hokkaido, the northern limit of the distribution of F. crenata on islands in the Japan Sea is observed on Okushiri Island (ca 42°N). To understand the genetic relationships of F. crenata on Okushiri Island, we examined chloroplast (cp) DNA haplotypes and 11 nuclear microsatellite (SSR) loci among 1,838 individuals from 44 populations from Okushiri Island, mainland Hokkaido, and the northern part of the Tohoku region on Honshu Island. We identified 2 cpDNA haplotypes, which represent not only populations on the Japan Sea coast but also those on the Pacific coast and this suggested the Okushiri Island populations might not be formed by single colonization. Genetic diversity of the Okushiri Island populations of nuclear SSR was not lower than the mainland and the STRUCTURE analysis revealed the Okushiri Island individuals were admixed between Hokkaido and Tohoku clusters. Approximate Bayesian computation inferred that divergence between Tohoku and Hokkaido, and admixture between two populations which generated Okushiri populations occurred before the last glacial maximum (LGM), that is, 7,890 (95% hyper probability density (HPD): 3,420 – 9,910) and 3,870 (95% HPD: 431– 8,540) generations ago, respectively. These inferences were well supported by a geological history which suggested an isolation of Okushiri Island from Hokkaido started prior to the Middle Pleistocene. We discuss the possible persistence of F. crenata during the last glacial maximum on northern islands in the Japan Sea such as Okushiri Island.
Psychosocial and bioethical challenges and developments for the future of vascularized composite allotransplantation: A scoping review and viewpoint of recent developments and clinical experiences in the field of vascularized composite allotransplantation
Authors: Kumnig Martin , Jowsey-Gregoire Sheila G. , Gordon Elisa J. , Werner-Felmayer Gabriele
Published: December 2022

Vascularized Composite Allotransplantation (VCA) has evolved in recent years, encompassing hand, face, uterus, penile, and lower extremity transplantation. Accordingly, without centralized oversight by United States Organ Procurement and Transplantation Network (OPTN) or European Programs, centers have developed their own practices and procedures that likely vary, and accordingly, present different levels of rigor to the evaluation process, internationally. The importance of psychosocial factors in the selection process and treatment course has been widely recognized, and therefore, several approaches have been developed to standardize and guide care of VCA candidates and recipients. We propose to develop an international multidisciplinary platform for the exchange of expertise that includes clinical, patient, and research perspectives. Patient perspectives would derive from peer education and the assessment of patient-reported outcomes. To establish a foundation for such a platform, future research should review and combine current VCA protocols, to develop the ethical framework for a standardized psychosocial evaluation and follow-up of VCA candidates and recipients. This review presents a comprehensive overview of recent results in the field of VCA, developments in structural aspects of VCA, and provides viewpoints driven from clinical experience.