bluuebunny/crossref_metadata_2025 huggingface dataset:
Damage-associated molecular patterns and sensing receptors based molecular subtypes in malignant pleural mesothelioma and implications for immunotherapy
Authors: Liu Zheng , Wan Rui , Bai Hua , Wang Jie
Published: March 2023

Objectives

Malignant pleural mesothelioma (MPM) is characterized as an incredibly aggressive form of cancer with a dismal diagnosis and a dearth of specific biomarkers and therapeutic options. For MPM patients, the effectiveness of immunotherapy may be influenced by damage-associated molecular pattern (DAMP)-induced immunogenic cell death (ICD).The objective of this work is to create a molecular profile associated with DAMPs to categorize MPM patients and predict their prognosis and response to immunotherapy.

Methods

The RNA-seq of 397 patients (263 patients with clinical data, 57.2% male, 73.0% over 60 yrs.) were gathered from eight public datasets as a training cohort to identify the DAMPs-associated subgroups of MPMs using K-means analysis. Three validation cohorts of patients or murine were established from TCGA and GEO databases. Comparisons were made across each subtype’s immune status, gene mutations, survival prognosis, and predicted response to therapy.

Results

Based on the DAMPs gene expression, MPMs were categorized into two subtypes: the nuclear DAMPs subtype, which is classified by the upregulation of immune-suppressed pathways, and the inflammatory DAMPs subtype, which is distinguished by the enrichment of proinflammatory cytokine signaling. The inflammatory DAMPs subgroup had a better prognosis, while the nuclear DAMPs subgroup exhibited a worse outcome. In validation cohorts, the subtyping system was effectively verified. We further identified the genetic differences between the two DAMPs subtypes. It was projected that the inflammatory DAMPs subtype will respond to immunotherapy more favorably, suggesting that the developed clustering method may be implemented to predict the effectiveness of immunotherapy.

Conclusion

We constructed a subtyping model based on ICD-associated DAMPs in MPM, which might serve as a signature to gauge the outcomes of immune checkpoint blockades. Our research may aid in the development of innovative immunomodulators as well as the advancement of precision immunotherapy for MPM.
Arenaviruses: Old viruses present new solutions for cancer therapy
Authors: Stachura Paweł , Stencel Olivia , Lu Zhe , Borkhardt Arndt , Pandyra Aleksandra A.
Published: March 2023

Viral-based cancer therapies have tremendous potential, especially in the context of treating poorly infiltrated cold tumors. However, in tumors with intact anti-viral interferon (IFN) pathways, while some oncolytic viruses induce strong innate and adaptive immune responses, they are neutralized before exerting their therapeutic effect. Arenaviruses, particularly the lymphocytic choriomeningitis virus (LCMV) is a noncytopathic virus with preferential cancer tropism and evolutionary mechanisms to escape the immune system for longer and to block early clearance. These escape mechanisms include inhibition of the MAVS dependent IFN pathway and spike protein antigen masking. Regarding its potential for cancer treatment, LCMV is therefore able to elicit long-term responses within the tumor microenvironment (TME), boost anti-tumor immune responses and polarize poorly infiltrating tumors towards a hot phenotype. Other arenaviruses including the attenuated Junin virus vaccine also have anti-tumor effects. Furthermore, the LCMV and Pichinde arenaviruses are currently being used to create vector-based vaccines with attenuated but replicating virus. This review focuses on highlighting the potential of arenaviruses as anti-cancer therapies. This includes providing a molecular understanding of its tropism as well as highlighting past and present preclinical and clinical applications of noncytophatic arenavirus therapies and their potential in bridging the gap in the treatment of cancers weakly responsive or unresponsive to oncolytic viruses. In summary, arenaviruses represent promising new therapies to broaden the arsenal of anti-tumor therapies for generating an immunogenic tumor microenvironment
Risk stratification based on DNA damage-repair-related signature reflects the microenvironmental feature, metabolic status and therapeutic response of breast cancer
Authors: Li Chunzhen , Yu Shu , Chen Jie , Hou Qianshan , Wang Siyi , Qian Cheng , Yin Shulei
Published: March 2023

DNA damage-repair machinery participates in maintaining genomic integrity and affects tumorigenesis. Molecular signatures based on DNA damage-repair-related genes (DRGs) capable of comprehensively indicating the prognosis, tumor immunometabolic profile and therapeutic responsiveness of breast cancer (BRCA) patients are still lacking. Integrating public datasets and bioinformatics algorithms, we developed a robust prognostic signature based on 27 DRGs. Multiple patient cohorts identified significant differences in various types of survival between high- and low-risk patients stratified by the signature. The signature correlated well with clinicopathological factors and could serve as an independent prognostic indicator for BRCA patients. Furthermore, low-risk tumors were characterized by more infiltrated CD8+ T cells, follicular helper T cells, M1 macrophages, activated NK cells and resting dendritic cells, and fewer M0 and M2 macrophages. The favorable immune infiltration patterns of low-risk tumors were also accompanied by specific metabolic profiles, decreased DNA replication, and enhanced antitumor immunity. Low-risk patients may respond better to immunotherapy, and experience improved outcomes with conventional chemotherapy or targeted medicine. Real-world immunotherapy and chemotherapy cohorts verified the predictive results. Additionally, four small molecule compounds promising to target high-risk tumors were predicted. In vitro experiments confirmed the high expression of GNPNAT1 and MORF4L2 in BRCA tissues and their association with immune cells, and the knockdown of these two DRGs suppressed the proliferation of human BRCA cells. In summary, this DNA damage-repair-related signature performed well in predicting patient prognosis, immunometabolic profiles and therapeutic sensitivity, hopefully contributing to precision medicine and new target discovery of BRCA.
Microstructures, absorption and adhesion evolution of FeCoCr/silicone resin coatings at elevated temperature
Authors: Yuan Dachao , Chen Zhiyong , Cai Changwei , Yang Bolin , Wang Yujie , Chen Zhihong
Published: March 2023

Heat-resistant magnetic microwave absorption coatings are vital important for the stealth safety of apparatus working at elevated temperature or electromagnetic compatibility of high density/power electronic devices. In this work, we proposed a heat-resistant coating with nanocrystalline FeCoCr micropowders as the absorbents and silicone resin as the matrix. The evolution of microstructure, absorption and adhesion of FeCoCr/silicone resin coatings were investigated after heat treatment at 400°C. The results show that the roughness of FeCoCr powders slightly increased due to the formation of nanoparticles, while their crystalline phase maintained body-centered cubic structure with grain size increasing from 10.8 nm to 18.1 nm after heat treatment. The saturated magnetization and coercivity of FeCoCr powders also increased after heat treatment. The adhesion of FeCoCr/silicone resin coatings exhibited sharp increase with the extension of heat treatment time, i.e., from 7.59 MPa at room temperature to 11.78 MPa after heat treatment at 400°C for 10 h; this phenomenon occurred due to the condense of FeCoCr-resin interfaces. The complex permittivity of the coating was reduced after heat treatment, while the complex permeability increased; this gave rise to enhancement of microwave absorption and showed the working potential of the FeCoCr/silicone resin coatings at elevated temperature.
Effect of vitamin D status on adult COVID-19 pneumonia induced by Delta variant: A longitudinal, real-world cohort study
Authors: Huang Hua , Zheng Jiawei , Liu Yan , Zhou Qunhe , Peng Denggao
Published: March 2023

Objective

The effect of vitamin D status on adult COVID-19 pneumonia induced by Delta variant remains to be further explored.

Methods

A longitudinal, real-world cohort study was performed. Artificial intelligence (AI) was used to identify and measure pneumonia lesions. All cases with pneumonia were divided into the vitamin D deficiency (VDD) and control groups according to serum 25-hydroxyvitamin D concentration. Lesion dynamics were observed within six time periods after the onset of pneumonia.

Results

A total of 161 cases were included, of which 101 (63%) were male and 46 (29%) presented with pneumonia. The median age and baseline 25-hydroxyvitamin D concentrations were 37 years and 21 ng/ml, respectively. Age, fibrinogen, and SARS-CoV-2 IgG titer on admission were independent predictors for the onset of pneumonia. After the onset of pneumonia, patients in the VDD group (n = 18) had higher percentage of fever (33 vs. 7.1%; p = 0.04) than those in the control group (n = 28); the interval of pneumonia resolution was longer (28 vs. 21 days; p = 0.02); lesions progressed more rapidly (p = 0.01) within 3 to 7 days and improved more slowly (p = 0.007) within more than 28 days; notably, simultaneous interleukin-6 (18.7 vs. 14.6 pg/ml; p = 0.04) levels were higher, and cycle thresholds for N gene (22.8 vs. 31.3; p = 0.04) and ORF1ab gene (20.9 vs. 28.7; p = 0.03) were lower within 3 to 7 days.

Conclusion

Vitamin D status may have effects on the progression and resolution, but not the onset of Delta variant-induced pneumonia in adults. Computed tomography image diagnosis system based on AI may have promising applications in the surveillance and diagnosis of novel SARS-CoV-2 variant-induced pneumonia.
Anaerobic fermentation featuring wheat bran and rice bran realizes the clean transformation of Chinese cabbage waste into livestock feed
Authors: Li Jiawei , Wang Cheng , Zhang Shanshan , Xing Jinxu , Song Chunsheng , Meng Qingwei , Li Jianping , Jia Shuo , Shan Anshan
Published: March 2023

Rapid aerobic decomposition and a high cost/benefit ratio restrain the transformation of Chinese cabbage waste into livestock feed. Herein, anaerobically co-fermenting Chinese cabbage waste with wheat bran and rice bran at different dry matter levels (250, 300, 350 g/kg fresh weight) was employed to achieve the effective and feasible clean transformation of Chinese cabbage waste, and the related microbiological mechanisms were revealed by high-throughput sequencing technology. The bran treatments caused an increase in pH value (4.75–77.25%) and free amino acid content (12.09–152.66%), but a reduction in lactic acid concentration (54.58–77.25%) and coliform bacteria counts (15.91–20.27%). In addition, the wheat bran treatment improved the levels of short-chain fatty acids, nonprotein nitrogen, water-soluble carbohydrates and antioxidant activity and reduced the ammonia nitrogen contents. In contrast, the rice bran treatment decreased the levels of acetic acid, water-soluble carbohydrates, nonprotein nitrogen, ammonia nitrogen, and antioxidant activities. Microbiologically, the bran treatments stimulated Pediococcus, Lactobacillus, Enterobacter, and Weissella but inhibited Lactococcus and Leuconostoc, which were the primary organic acid producers reflected by the redundancy analysis. In addition, Chinese cabbage waste fermented with wheat bran at 350 g/kg fresh weight or with rice bran at 300 g/kg fresh weight increased the scale and complexity of bacteriome, promoted commensalism or mutualism and upregulated the global metabolism pathways, including carbohydrate and amino acid metabolisms. Furthermore, the bran treatments resulted in an increase in bacterial communities that were facultatively anaerobic, biofilm-formed, Gram-negative, potentially pathogenic and stress-tolerant. Collectively, the bran treatments inhibited effluent formation and protein degradation and improved nutrient preservation but reduced organic acid production during the anaerobic fermentation, which is linked to the variations in the bacteriome, indicating that the constructed fermentation system should be further optimized.
Relationships between fungal diversity and fruit quality of Yuluxiang pear during low temperature storage
Authors: Hou Yaru , Zhang Xiaoyu , Gao Zhenfeng , Chen Tian , Zhang Lixin
Published: March 2023

Postharvest decay is an urgent problem that affects the storage of pears. Low temperature storage is one of the most important methods to reduce the prevalence of fruit diseases during storage. In this study, the microbial diversity of postharvest Yuluxiang pear (Pyrus × michauxii “Yu Lu Xiang”) fruits stored at low temperature for different lengths of times was analyzed. Illumina MiSeq high-throughput sequencing was used to analyze the composition and diversity of fungal communities. The results showed that the fungi within fruit were classified into 6 phyla, 18 classes, 40 orders, 72 families, and 92 genera based on the 97% sequence similarity level. They belonged to 6 phyla, 18 classes, 40 orders, 72 families, and 92 genera. The highest richness of fungi was obtained after 30 d of treatment. The β-diversity index showed that the fungal community composition of these fruit was significantly different at the beginning of storage compared with the different timepoints of samples at low temperature during storage. The comparison of fungal composition at the phylum level indicated that Ascomycota was dominant in the different timepoints of samples at low temperature, while Alternaria was the primary fungus at the genus level. A correlation analysis was used to further explore the correlation between fungi and fruit firmness, titratable acid, and solid soluble contents at low temperatures during storage. Aureobasidium and Didymella positively correlated with the soluble solids and hardness. Phoma positively correlated with the titratable acid, and Aspergillus positively correlated with titratable acid and hardness. This study can guide the industrial production of Yulu pear and also provide a theoretical basis to prevent and control diseases during the storage period of Yulu pear.
“Candidatus Hydrogenisulfobacillus filiaventi” strain R50 gen. nov. sp. nov., a highly efficient producer of extracellular organic compounds from H2 and CO2
Authors: Hogendoorn Carmen , Pol Arjan , de Graaf Rob , White Paul B. , Mesman Rob , van Galen Peter M. , van Alen Theo A. , Cremers Geert , Jansen Robert S. , Jetten Mike S. M. , Op den Camp Huub J. M.
Published: March 2023

Production of organic molecules is largely depending on fossil fuels. A sustainable alternative would be the synthesis of these compounds from CO2 and a cheap energy source, such as H2, CH4, NH3, CO, sulfur compounds or iron(II). Volcanic and geothermal areas are rich in CO2 and reduced inorganic gasses and therefore habitats where novel chemolithoautotrophic microorganisms for the synthesis of organic compounds could be discovered. Here we describe “Candidatus Hydrogenisulfobacillus filiaventi” R50 gen. nov., sp. nov., a thermoacidophilic, autotrophic H2-oxidizing microorganism, that fixed CO2 and excreted no less than 0.54 mol organic carbon per mole fixed CO2. Extensive metabolomics and NMR analyses revealed that Val, Ala and Ile are the most dominant form of excreted organic carbon while the aromatic amino acids Tyr and Phe, and Glu and Lys were present at much lower concentrations. In addition to these proteinogenic amino acids, the excreted carbon consisted of homoserine lactone, homoserine and an unidentified amino acid. The biological role of the excretion remains uncertain. In the laboratory, we noticed the production under high growth rates (0.034 h−1, doubling time of 20 h) in combination with O2-limitation, which will most likely not occur in the natural habitat of this strain. Nevertheless, this large production of extracellular organic molecules from CO2 may open possibilities to use chemolithoautotrophic microorganisms for the sustainable production of important biomolecules.
Abnormal intra- and inter-network functional connectivity of brain networks in early-onset Parkinson’s disease and late-onset Parkinson’s disease
Authors: Zhou Fan , Tan ChangLian , Song Chendie , Wang Min , Yuan Jiaying , Liu Yujing , Cai Sainan , Liu QinRu , Shen Qin , Tang Yuqing , Li Xu , Liao Haiyan
Published: March 2023

Objective

The purpose of this study is to look into the altered functional connectivity of brain networks in Early-Onset Parkinson’s Disease (EOPD) and Late-Onset Parkinson’s Disease (LOPD), as well as their relationship to clinical symptoms.

Methods

A total of 50 patients with Parkinson’ disease (28 EOPD and 22 LOPD) and 49 healthy controls (25 Young Controls and 24 Old Controls) were admitted to our study. Employing independent component analysis, we constructed the brain networks of EOPD and Young Controls, LOPD and Old Controls, respectively, and obtained the functional connectivity alterations in brain networks.

Results

Cerebellar network (CN), Sensorimotor Network (SMN), Executive Control Network (ECN), and Default Mode Network (DMN) were selected as networks of interest. Compared with their corresponding health controls, EOPD showed increased functional connectivity within the SMN and ECN and no abnormalities of inter-network functional connectivity were found, LOPD demonstrated increased functional connectivity within the ECN while decreased functional connectivity within the CN. Furthermore, in LOPD, functional connectivity between the SMN and DMN was increased. The functional connectivity of the post-central gyrus within the SMN in EOPD was inversely correlated with the Unified Parkinson’s Disease Rating Scale Part III scores. Age, age of onset, and MMSE scores are significantly different between EOPD and LOPD (p < 0.05).

Conclusion

There is abnormal functional connectivity of networks in EOPD and LOPD, which could be the manifestation of the associated pathological damage or compensation.
LVIS-within-enterprise double-stent technique with coil embolization in the treatment of patients with acutely ruptured intracranial vertebrobasilar artery-dissecting aneurysms
Authors: Wu Qiaowei , Meng Yuxiao , Chen Aixia , Xu Shancai , Wang Chunlei , Ji Zhiyong , Qi Jingtao , Yuan Kaikun , Shao Jiang , Shi Huaizhang , Wu Pei
Published: March 2023

Objective

This study aimed to evaluate the feasibility of the low-profile visualized intraluminal support (LVIS)-within-enterprise double-stent technique for patients with acutely ruptured intracranial vertebrobasilar artery-dissecting aneurysms (ari-VBDAs).

Methods

A total of 30 patients with ari-VBDAs who underwent reconstructive treatment using LVIS-within-enterprise double-stent technique with coil embolization between January 2014 and May 2022 were retrospectively enrolled. Patients' characteristics and clinical and imaging outcomes were reviewed. The functional outcomes were assessed using the modified Rankin scale (mRS).

Results

A total of 34 ari-VBDAs were identified, including seven (20.6%) basilar artery aneurysms and 27 (79.4%) vertebral artery aneurysms. All aneurysms were successfully treated in the acute phase. In total, six (20.0%) patients experienced in-hospital serious adverse events, including two deaths (6.7%). The median clinical follow-up time of the remaining 28 patients was 20.0 (IQR, 7.3–40.8) months. The incidences of dependency or death (mRS score of 3–6) at discharge and at the last follow-up were 16.7% and 14.3%, respectively. Aneurysm rebleeding occurred in one (3.3%) patient periprocedurally. In total, three (10.0%) patients had ischemic events, one of which occurred during the periprocedural period and two occurred during follow-up. A total of two patients (6.7%) underwent ventriculoperitoneal shunt. Imaging follow-up was available for 14 patients at the median of 12.0 (IQR, 7.0–12.3) months, with a complete occlusion rate of 93.3% (14/15). In total, one patient experienced parent artery occlusion, and no aneurysm was recanalized.

Conclusion

LVIS-within-enterprise double-stent technique with coil embolization for the treatment of patients with ari-VBDAs could be performed with a good safety profile and high technical success rate. The rate of complete aneurysm occlusion during follow-up seemed to be satisfactory.
Unexpected cardiorespiratory findings postictally and at rest weeks prior to SUDEP
Authors: Lamrani Yassine , Tran Thi Phuoc Yen , Toffa Dènahin Hinnoutondji , Robert Manon , Bérubé Arline-Aude , Nguyen Dang Khoa , Bou Assi Elie
Published: March 2023

Introduction

Mechanisms underlying sudden unexpected death in epilepsy (SUDEP) are unclear, but autonomic disorders are thought to play a critical role. However, those dysfunctions have mainly been reported in the peri-ictal context of generalized tonic–clonic seizures. Here, we explored whether heart rate variability (HRV), heart rate (HR), and breathing rate (BR) changes could be observed perictally during focal seizures with or without impaired awareness as well as interictally to assess the risk of SUDEP. We report the case of a 33-year-old patient with drug-resistant bilateral temporal lobe epilepsy who died at home probably from an unwitnessed nocturnal seizure (“probable SUDEP”).

Methods

Ictal and interictal HRV as well as postictal cardiorespiratory analyses were conducted to assess autonomic functions and overall SUDEP risk. The SUDEP patient was compared to two living male patients from our local database matched for age, sex, and location of the epileptic focus.

Results

Interictal HRV analysis showed that all sleep HRV parameters and most awake HRV parameters of the SUDEP patient were significantly lower than those of our two control subjects with bitemporal lobe epilepsy without SUDEP (p < 0.01). In two focal with impaired awareness seizures (FIAS) of the SUDEP patient, increased postictal mean HR and reduced preictal mean high frequency signals (HF), known markers of increased seizure severity in convulsive seizures, were seen postictally. Furthermore, important autonomic instability and hypersensitivity were seen through fluctuations in LF/HF ratio following two seizures of the SUDEP patient, with a rapid transition between sympathetic and parasympathetic activity. In addition, a combination of severe hypopnea (202 s) and bradycardia (10 s), illustrating autonomic dysfunction, was found after one of the SUDEP patient’s FIAS.

Discussion

The unusual cardiorespiratory and HRV patterns found in this case indicated autonomic abnormalities that were possibly predictive of an increased risk of SUDEP. It will be interesting to perform similar analyses in other SUDEP cases to see whether our findings are anecdotal or instead suggestive of reliable biomarkers of high SUDEP risk in focal epilepsy, in particular focal with or without impaired awareness seizures.
Clinical features of minor hallucinations in different phenotypes of Parkinson’s disease: A cross-sectional study
Authors: Wang Yaxi , Li Dongfeng , Chen Yaning , Zhu Sha , Jiang Xu , Jiang Yinyin , Gu Ruxin , Shen Bo , Zhu Jun , Pan Yang , Yan Jun , Zhang Li
Published: March 2023

Background

Minor hallucinations (MHs) are the most common psychiatric symptom associated with Parkinson’s disease (PDPsy), but little is known about their characteristics in different motor phenotypes, especially postural instability gait difficulty (PIGD). The aim of this study was to explore the clinical features of MHs in different subtypes of PD.

Methods

In this cross-sectional study, 213 patients with Parkinson’s disease (PD) were recruited, and the data obtained included comprehensive demographics, motor subtypes, clinical scale scores, and MH contents. Motor subtypes were classified as tremor-dominant (TD), PIGD or indeterminate according to Stebbins’ method.

Results

A total of 213 PD patients were included: 90 (42.3%) TD patients, 98 (46.0%) PIGD patients and 25 (11.7%) indeterminate. In total, 70 (32.9%) patients experienced MHs. Compared to patients with the TD phenotype, we found that patients with the PIGD phenotype had more severe motor and nonmotor symptoms. They also had a higher incidence of visual illusions (VIs) and a shorter MH latency.

Conclusion

Our study demonstrated that compared to patients with the TD phenotype, patients with the PIGD phenotype had a higher incidence of MHs, especially VIs, which may lead to a higher incidence of visual hallucinations (VHs). They also had a shorter latency of MHs than patients with the TD phenotype, suggesting an earlier onset of MHs and a worse prognosis.
Neurointerface with oscillator motifs for inhibitory effect over antagonist muscles
Authors: Mikhailova Yulia , Pozdeeva Anna , Suleimanova Alina , Leukhin Alexey , Toschev Alexander , Lukmanov Timur , Fatyhova Elsa , Magid Evgeni , Lavrov Igor , Talanov Max
Published: March 2023

The effect of inhibitory management is usually underestimated in artificial control systems, using biological analogy. According to our hypothesis, the muscle hypertonus could be effectively compensated via stimulation by bio-plausible patterns. We proposed an approach for the compensatory stimulation device as implementation of previously presented architecture of the neurointerface, where (1) the neuroport is implemented as a DAC and stimulator, (2) neuroterminal is used for neurosimulation of a set of oscillator motifs on one-board computer. In the set of experiments with five volunteers, we measured the efficacy of motor neuron inhibition via the antagonist muscle or nerve stimulation registering muscle force with and without antagonist stimulation. For the agonist activation, we used both voluntary activity and electrical stimulation. In the case of stimulation of both the agonist and the antagonist muscles and nerves, we experimented with delays between muscle stimulation in the range of 0–20 ms. We registered the subjective discomfort rate. We did not identify any significant difference between the antagonist muscle and nerve stimulation in both voluntary activity and electrical stimulation of cases showing agonist activity. We determined the most effective delay between the stimulation of the agonist and the antagonist muscles and nerves as 10–20 ms.
Comparison of differential metabolites in brain tissue of aged marmosets and serum of elderly patients after prolonged anesthesia
Authors: Zhang Fengwei , Mao Haoli , Zhu Jiao , Zhou Ren , Zhang Lei , Jiang Hong
Published: March 2023

Objective

To compare the differential metabolites in the brain tissue of aged marmosets after long-term anesthesia (≥ 6 h) and the serum of elderly patients by metabolomics methods.

Methods

Six aged marmosets (≥ 8 years old) were divided into two groups: anesthesia and control. The aged monkeys in the anesthesia group were induced with 6–8% sevoflurane and 100% oxygen (2 l/min) for 1–2 min and maintained with 1.5–2.5% sevoflurane and 100% oxygen (2 l/min) for 6 h. In the control group (n = 3), anesthesia was only induced under the same conditions for 1–2 min. The prefrontal cortex tissues of the two groups of aged marmosets were collected for metabolomics detection. Twenty-nine elderly patients (≥ 65 years old) who had undergone surgical anesthesia for more than 6 h were enrolled. Serum samples were collected before and on the first day after surgery for metabolomics analysis. Differential metabolites were compared between human serum and marmoset brain tissue.

Results

The changes in lactate and xanthurenic acid in the serum of elderly patients were consistent with those in the brain tissue of aged marmoset monkeys, that is, lactate was up-regulated and xanthurenic acid was down-regulated. However, serum levels of 5-methylterahydrofolic acid and leucine were down-regulated in elderly patients after anesthesia. In contrast, 5-methylterahydrofolic acid and leucine levels were up-regulated in the prefrontal cortex of aged marmosets compared with control marmosets. Furthermore, glycolysis/gluconeogenesis and pentose phosphate pathway were both significantly enriched in the prefrontal cortex of aged marmosets and serum of elderly patients after surgery.

Conclusion

The changes of serum metabolites in elderly patients are not exactly the same as the metabolic changes of brain tissues in aged marmosets. The metabolic changes in serum lactate and xanthurenic acid levels can reflect brain tissue metabolism. The enrichment pathways of differential metabolites in the serum of elderly patients and the brain tissue of aged marmosets were partially the same.
Impact of intravenous vitamin C as a monotherapy on mortality risk in critically ill patients: A meta-analysis of randomized controlled trials with trial sequential analysis
Authors: Hung Kuo-Chuan , Chuang Min-Hsiang , Chen Jen-Yin , Hsu Chih-Wei , Chiu Chong-Chi , Chang Ying-Jen , Lee Chia-Wei , Chen I-Wen , Sun Cheuk-Kwan
Published: March 2023

Background

This meta-analysis aimed at investigating the pooled evidence regarding the effects of intravenous vitamin C (IVVC) on mortality rate in critically ill patients.

Methods

Databases including Medline, Embase, and Cochrane Library were searched from inception to October, 2022 to identify RCTs. The primary outcome was the risk of overall mortality. Subgroup analyses were performed based on IVVC dosage (i.e., cut-off value: 100 mg/kg/day or 10000 mg/day). Trial sequential analysis (TSA) was used to examine the robustness of evidence.

Results

A total of 12 trials including 1,712 patients were analyzed. Although meta-analysis demonstrated a lower risk of mortality in patients with IVVC treatment compared to those without [risk ratio (RR): 0.76, 95% CI: 0.6 to 0.97, p = 0.02, I2 = 36%, 1,711 patients), TSA suggested the need for more studies for verification. Moreover, subgroup analyses revealed a reduced mortality risk associated with a low IVVC dosage (RR = 0.72, p = 0.03, 546 patients), while no beneficial effect was noted with high IVVC dosage (RR = 0.74, p = 0.13, I2 = 60%, 1,165 patients). The durations of vasopressor [mean difference (MD): −37.75 h, 404 patients) and mechanical ventilation (MD: −47.29 h, 388 patients) use were shorter in the IVVC group than those in the controls, while there was no significant difference in other prognostic outcomes (e.g., length of stay in intensive care unit/hospital) between the two groups.

Conclusion

Although intravenous vitamin C as a monotherapy reduced pooled mortality, durations of vasopressor use and mechanical ventilation, further research is required to support our findings and to identify the optimal dosage of vitamin C in the critical care setting.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022371090.
Integrated bioinformatic analysis and cell line experiments reveal the significant role of the novel immune checkpoint TIGIT in kidney renal clear cell carcinoma
Authors: Xia Qi-Dong , Li Bo , Sun Jian-Xuan , Liu Chen-Qian , Xu Jin-Zhou , An Ye , Xu Meng-Yao , Zhang Si-Han , Zhong Xing-Yu , Zeng Na , Ma Si-Yang , He Hao-Dong , Zhang Yu-Cong , Guan Wei , Li Heng , Wang Shao-Gang
Published: March 2023

Background

T cell immunoglobulin and ITIM domain (TIGIT) is a widely concerned immune checkpoint, which plays an essential role in immunosuppression and immune evasion. However, the role of TIGIT in normal organ tissues and renal clear cell carcinoma is unclear. We aim to identify the critical role of TIGIT in renal clear cell carcinoma and find potential targeted TIGIT drugs.

Materials and methods

Data retrieved from the GTEX database and TCGA database was used to investigate the expression of TIGIT in normal whole-body tissues and abnormal pan-cancer, then the transcriptome atlas of patients with kidney renal clear cell carcinoma (KIRC) in the TCGA database were applied to distinguish the TIGIT related features, including differential expression status, prognostic value, immune infiltration, co-expression, and drug response of sunitinib an anti-PD1/CTLA4 immunotherapy in KIRC. Furthermore, we constructed a gene-drug network to discover a potential drug targeting TIGIT and verified it by performing molecular docking. Finally, we conducted real-time polymerase chain reaction (PCR) and assays for Transwell migration and CCK-8 to explore the potential roles of TIGIT.

Results

TIGIT showed a moderate expression in normal kidney tissues and was confirmed as an essential prognostic factor that was significantly higher expressed in KIRC tissues, and high expression of TIGIT is associated with poor OS, PFS, and DSS in KIRC. Also, the expression of TIGIT was closely associated with the pathological characteristics of the tumor, high expression of TIGIT in KIRC was observed with several critical functions or pathways such as apoptosis, BCR signaling, TCR signaling et al. Moreover, the expression of TIGIT showed a strong positive correlation with infiltration of CD8+ T cells and Tregs and a positive correlation with the drug sensitivity of sunitinib simultaneously. Further Tide ips score analysis and submap analysis reveal that patients with high TIGIT expression significantly show a better response to anti-PD1 immunotherapy. Following this, we discovered Selumetinib and PD0325901 as potential drugs targeting TIGIT and verified the interaction between these two drugs and TIGIT protein by molecular docking. Finally, we verified the essential role of TIGIT in the proliferation and migration functions by using KIRC cell lines.

Conclusions

TIGIT plays an essential role in tumorigenesis and progression in KIRC. High expression of TIGIT results in poor survival of KIRC and high drug sensitivity to sunitinib. Besides, Selumetinib and PD0325901 may be potential drugs targeting TIGIT, and combined therapy of anti-TIGIT and other treatments show great potential in treating KIRC.
Application status and future prospects of the PDX model in lung cancer
Authors: Liu Wei , Cui Yishuang , Zheng Xuan , Yu Kunpeng , Sun Guogui
Published: March 2023

Lung cancer is one of the most prevalent, fatal, and highly heterogeneous diseases that, seriously threaten human health. Lung cancer is primarily caused by the aberrant expression of multiple genes in the cells. Lung cancer treatment options include surgery, radiation, chemotherapy, targeted therapy, and immunotherapy. In recent decades, significant progress has been made in developing therapeutic agents for lung cancer as well as a biomarker for its early diagnosis. Nonetheless, the alternative applications of traditional pre-clinical models (cell line models) for diagnosis and prognosis prediction are constrained by several factors, including the lack of microenvironment components necessary to affect cancer biology and drug response, and the differences between laboratory and clinical results. The leading reason is that substantial shifts accrued to cell biological behaviors, such as cell proliferative, metastatic, invasive, and gene expression capabilities of different cancer cells after decades of growing indefinitely in vitro. Moreover, the introduction of individualized treatment has prompted the development of appropriate experimental models. In recent years, preclinical research on lung cancer has primarily relied on the patient-derived tumor xenograft (PDX) model. The PDX provides stable models with recapitulate characteristics of the parental tumor such as the histopathology and genetic blueprint. Additionally, PDXs offer valuable models for efficacy screening of new cancer drugs, thus, advancing the understanding of tumor biology. Concurrently, with the heightened interest in the PDX models, potential shortcomings have gradually emerged. This review summarizes the significant advantages of PDXs over the previous models, their benefits, potential future uses and interrogating open issues.
The RNA helicase DDX3 and its role in c-MYC driven germinal center-derived B-cell lymphoma
Authors: Lacroix Marion , Beauchemin Hugues , Khandanpour Cyrus , Möröy Tarik
Published: March 2023

DDX3X is an RNA helicase with many functions in RNA metabolism such as mRNA translation, alternative pre-mRNA splicing and mRNA stability, but also plays a role as a regulator of transcription as well as in the Wnt/beta-catenin- and Nf-κB signaling pathways. The gene encoding DDX3X is located on the X-chromosome, but escapes X-inactivation. Hence females have two active copies and males only one. However, the Y chromosome contains the gene for the male DDX3 homologue, called DDX3Y, which has a very high sequence similarity and functional redundancy with DDX3X, but shows a more restricted protein expression pattern than DDX3X. High throughput sequencing of germinal center (GC)-derived B-cell malignancies such as Burkitt Lymphoma (BL) and Diffuse large B-cell lymphoma (DLBCL) samples showed a high frequency of loss-of-function (LOF) mutations in the DDX3X gene revealing several features that distinguish this gene from others. First, DDX3X mutations occur with high frequency particularly in those GC-derived B-cell lymphomas that also show translocations of the c-MYC proto-oncogene, which occurs in almost all BL and a subset of DLBCL. Second, DDX3X LOF mutations occur almost exclusively in males and is very rarely found in females. Third, mutations in the male homologue DDX3Y have never been found in any type of malignancy. Studies with human primary GC B cells from male donors showed that a loss of DDX3X function helps the initial process of B-cell lymphomagenesis by buffering the proteotoxic stress induced by c-MYC activation. However, full lymphomagenesis requires DDX3 activity since an upregulation of DDX3Y expression is invariably found in GC derived B-cell lymphoma with DDX3X LOF mutation. Other studies with male transgenic mice that lack Ddx3x, but constitutively express activated c-Myc transgenes in B cells and are therefore prone to develop B-cell malignancies, also showed upregulation of the DDX3Y protein expression during the process of lymphomagenesis. Since DDX3Y is not expressed in normal human cells, these data suggest that DDX3Y may represent a new cancer cell specific target to develop adjuvant therapies for male patients with BL and DLBCL and LOF mutations in the DDX3X gene.
Calcium signalling in weeds under herbicide stress: An outlook
Authors: Hamouzová Katerina , Sen Madhab Kumar , Bharati Rohit , Košnarová Pavlína , Chawdhery Md Rafique Ahasan , Roy Amit , Soukup Josef
Published: March 2023

The continuous use of herbicides for controlling weeds has led to the evolution of resistance to all major herbicidal modes of action globally. Every year, new cases of herbicide resistance are reported. Resistance is still in progress in many species, which must be stopped before it becomes a worldwide concern. Several herbicides are known to cause stressful conditions that resemble plant abiotic stresses. Variation in intracellular calcium (Ca2+) concentration is a primary event in a wide range of biological processes in plants, including adaptation to various biotic and abiotic stresses. Ca2+ acts as a secondary messenger, connecting various environmental stimuli to different biological processes, especially during stress rejoindering in plants. Even though many studies involving Ca2+ signalling in plants have been published, there have been no studies on the roles of Ca2+ signalling in herbicide stress response. Hence, this mini-review will highlight the possible sensing and molecular communication via Ca2+ signals in weeds under herbicide stress. It will also discuss some critical points regarding integrating the sensing mechanisms of multiple stress conditions and subsequent molecular communication. These signalling responses must be addressed in the future, enabling researchers to discover new herbicidal targets.
Different photosynthetic inorganic carbon utilization strategies in the heteroblastic leaves of an aquatic plant Ottelia ovalifolia
Authors: Liao Zuying , Li Pengpeng , Zhou Jingzhe , Li Wei , Jiang Hong Sheng
Published: March 2023

The leaves of the heteroblastic aquatic plant Ottelia ovalifolia faces submerged and aerial environments during its life history. However, the acclimation of the submerged leaves and floating leaves to these two environments in morphology, physiology, and biochemistry remain unclear. In the present study, we investigated the acclimation of the CO2-concentrating mechanisms in these two types of leaves. We found that the submerged leaves were longer, narrower, and thinner than the floating leaves, which increased the specific surface area of the leaves and lead to better absorption of the inorganic carbon underwater. Meanwhile, the floating leaves absorbed atmospheric CO2 directly through the stomata to acclimate to the aerial environment. Both the leaf types had the ability to use HCO3−, but the capacity in submerged leaves was stronger than that in floating leaves. The extracellular carbonic anhydrase and anion exchanger were responsible for the HCO3− use in both types of leaves. The higher ratio of chlorophyll a/b and content of anthocyanin in floating leaves than that in submerged leaves indicated that the acclimation of aerial and submerged photosynthesis depended on changes in the photosynthetic pigments. Based on the stable carbon isotope ratio, key enzyme activities of the C4 pathway indicated that submerged leaves might have the ability to perform C4 metabolism while floating leaves only performed C3 metabolism. In summary, O. ovalifolia acclimates to submerged and aerial environments through changes in morphology, physiology, and biochemistry during different growth stages.
Activation and tolerance of Siegesbeckia Orientalis L. rhizosphere to Cd stress
Authors: Xie Jianyu , Xu Xiaoxun , Zhang Shirong , Yang Zhanbiao , Wang Guiyin , Li Ting , Pu Yulin , Zhou Wei , Xu Changlian , Lv Guochun , Cheng Zhang , Xian Junren , Pu Zhien
Published: March 2023

This experiment investigated the changes of rhizosphere soil microenvironment for hyperaccumulation-soil system under Cd stress in order to reveal the mechanism of hyperaccumulation and tolerance. Thus, Cd fractions, chemical compositions, and biochemical characteristics in rhizosphere soil of Siegesbeckia orientalis L. under Cd stress conditions of 0, 5, 10, 25, 50, 100, and 150 mg kg-1 were investigated through a root bag experiment, respectively. As a result, Cd induced the acidification of S. orientalis rhizosphere soil, and promoted the accumulation of dissolved organic carbon (DOC) and readily oxidizable organic carbon (ROC), which increased by 28.39% and 6.98% at the maximum compared with control. The percentage of labile Cd (acid-soluble and reducible Cd) in soil solution increased significantly (P < 0.05) from 31.87% to 64.60% and from 26.00% to 34.49%, respectively. In addition, rhizosphere microenvironment can alleviate the inhibition of Cd on soil microorganisms and enzymes compare with bulk soils. Under medium and low concentrations of Cd, the rhizosphere soil microbial biomass carbon (MBC), basal respiration, ammonification and nitrification were significantly increased (P < 0.05), and the activities of key enzymes were not significantly inhibited. This suggests that pH reduction and organic carbon (DOC and ROC) accumulation increase the bioavailability of Cd and may have contributed to Cd accumulation in S. orientalis. Moreover, microorganisms and enzymes in rhizosphere soils can enhance S. orientalis tolerance to Cd, alleviating the nutrient imbalance and toxicity caused by Cd pollution. This study revealed the changes of physicochemical and biochemical properties of rhizosphere soil under Cd stress. Rhizosphere soil acidification and organic carbon accumulation are key factors promoting Cd activation, and microorganisms and enzymes are the responses of Cd tolerance.
Animal models of compulsion alcohol drinking: Why we love quinine-resistant intake and what we learned from it
Authors: De Oliveira Sergio Thatiane , Frasier Raizel M. , Hopf Frederic W.
Published: March 2023

Alcohol Use Disorder (AUD) ranks among the most prevalent mental disorders, extracting ~$250 billion/year in the US alone and producing myriad medical and social harms. Also, the number of deaths related to problem drinking has been increasing dramatically. Compulsive alcohol drinking, characterized by intake that persists despite negative consequences, can be particularly important and a major obstacle to treatment. With the number of people suffering from AUD increasing during the past years, there is a critical need to understand the neurobiology related to compulsive drives for alcohol, as well as the development of novel AUD pharmacological therapies. Here we discuss rodent compulsion-like alcohol drinking (CLAD) models, focusing on the two most widely used adverse stimuli to model rodent compulsion-like responding, quinine adulteration of alcohol and footshook-resistant alcohol intake. For both cases, the goal is to uncover behavior patterns and brain circuits that underlie drive for alcohol even in the face of negative consequences. We discuss caveats, benefits, and potential brain mechanisms, of models for consequence-resistant responding for alcohol more generally, and especially highlight some advantages of quinine-resistance over footshook-resistance. Further, since this review contributes to a Special issue focused on Molecular Aspects of Compulsive Drug Use, we discuss our new findings showing how the noradrenergic system is related to CLAD responding. In particular, we comment on the importance of α1 and β adrenergic receptors (ARs) as potential targets for treating AUD.
The research foundation for COVID-19 vaccine development
Authors: Messan Komi S. , Sulima Pawel P. , Ghosh Dolan , Nye Jonathan
Published: March 2023

The development of effective vaccines in <1 year to combat the spread of coronavirus disease 19 (COVID-19) is an example of particularly rapid progress in biomedicine. However, this was only made possible by decades of investment in scientific research. Many important research commentaries and reviews have been provided to describe the various contributions and scientific breakthroughs that led to the development of COVID-19 vaccines. In this work, we sought to complement those efforts by adding a systematic and quantitative study of the research foundations that led to these vaccines. Here, we analyzed citations from COVID-19 vaccine research articles to determine which scientific areas of study contributed the most to this research. Our findings revealed that coronavirus research was cited most often, and by a large margin. However, significant contributions were also seen from a diverse set of fields such as cancer, diabetes, and HIV/AIDS. In addition, we examined the publication history of the most prolific authors of COVID-19 vaccine research to determine their research expertise prior to the pandemic. Interestingly, although COVID-19 vaccine research relied most heavily on previous coronavirus work, we find that the most prolific authors on these publications most often had expertise in other areas including influenza, cancer, and HIV/AIDS. Finally, we used machine learning to identify and group together publications based on their major topic areas. This allowed us to elucidate the differences in citations between research areas. These findings highlight and quantify the relevance of prior research from a variety of scientific fields to the rapid development of a COVID-19 vaccine. This study also illustrates the importance of funding and sustaining a diverse research enterprise to facilitate a rapid response to future pandemics.