ABSTRACT
Lectin receptor-like kinase(LecRLK) is a class of phytokinase with lectin conserved domain, which plays an important role in plant resistance to biological and abiotic stresses, as well as plant growth and development. Cannabis sativa is an important multi-purpose plant, widely used in food, textile, medicine, and other fields. Genome-wide screening and expression analysis of the LecRLK family of C. sativa were performed in this paper, so as to provide scientific reference for functional analysis of the LecRLK family of C. sativa. Based on BLAST and HMM methods, 93 LecRLKs were identified in the whole genome of C. sativa, including 69 G types, 23 L types, and one C types. Subsequently, a series of bioinformatics analyses were performed on the LecRLK family members, and the physicochemical properties of the protein of the LecRLK family members were initially revealed. The prediction of cis-acting elements of promoters in family members showed that family members were regulated by hormones and stress response. The expression analysis showed that some family members were highly expressed in the roots, which may participate in the process of stress resistance. Several members were highly expressed in female flowers and may be involved in female flower development. This study provides a theoretical basis for further study of LecRLK gene function. Meanwhile, the expression analysis screens candidate LecRLK members who may participate in the resistance of C. sativa, which provides a theoretical basis for the subsequent selection of C. sativa varieties against resistance.
Subject(s)
Cannabis , Computational Biology , Gene Expression Regulation, Plant , Plant Proteins , Cannabis/genetics , Cannabis/growth & development , Cannabis/chemistry , Cannabis/enzymology , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Proteins/chemistry , Phylogeny , Multigene Family , Genome, Plant/geneticsABSTRACT
Importance: Recent changes in China's social medical insurance reimbursement policy have impacted the financial burden of patients with phenylketonuria (PKU) for special foods. However, whether this policy change is associated with their blood phenylalanine (PHE) concentration is unclear. Objective: To investigate the association between the reimbursement policy and blood PHE concentration in patients with PKU. Design, Setting, and Participants: This cohort study measured the blood PHE concentrations of 167 patients with PKU across 4 newborn screening centers in China from January 2018 to December 2021. The reimbursement policy for special foods for patients with PKU at 2 centers was canceled in 2019 and restored from 2020 onwards. In contrast, the other 2 centers consistently implemented the policy. Data were analyzed from September 10 to December 6, 2023. Exposures: The implementation and cancelation of the reimbursement policy for special foods of patients with PKU. Main Outcomes and Measures: The blood PHE concentration was regularly measured from 2018 to 2021. A 1-sided Z test was used to compare the mean of the blood PHE concentration between different years. Results: Among 167 patients with PKU (mean [SD] age, 84.4 [48.3] months; 87 males [52.1%]), a total of 4285 measurements of their blood PHE concentration were collected from 2018 to 2021. For patients at the center that canceled the reimbursement policy in 2019, the mean (SD) of the blood PHE concentrations in 2019 was 5.95 (5.73) mg/dL, significantly higher than 4.84 (4.11) mg/dL in 2018 (P < .001), 5.06 (5.21) mg/dL in 2020 (P = .006), and 4.77 (4.04) mg/dL in 2021 (P < .001). Similarly, for patients at the other center that canceled the policy in 2019, the mean (SD) of the blood PHE concentrations in 2019 was 5.95 (3.43) mg/dL, significantly higher than 5.34 (3.45) mg/dL in 2018 (P = .03), 5.13 (3.15) mg/dL in 2020 (P = .003), and 5.39 (3.46) mg/dL in 2021 (P = .03). On the contrary, no significant difference was observed between any of the years for patients at the 2 centers that consistently implemented the policy. Conclusions and Relevance: In this cohort study of patients with PKU from multiple centers, the implementation of the reimbursement policy for special foods was associated with controlling the blood PHE concentration. Special foods expenditure for patients with PKU should be included in the scope of long-term social medical insurance reimbursement.
Subject(s)
Insurance, Health, Reimbursement , Phenylalanine , Phenylketonurias , Humans , Phenylketonurias/blood , Phenylketonurias/economics , Phenylketonurias/diet therapy , Phenylalanine/blood , China , Male , Female , Insurance, Health, Reimbursement/statistics & numerical data , Neonatal Screening/economics , Neonatal Screening/methods , Infant, Newborn , Child, Preschool , Child , Foods, Specialized/economics , Cohort Studies , InfantABSTRACT
Human bocavirus 1 (HBoV1) is a human parvovirus that causes lower respiratory tract infections in young children. It contains a single-stranded (ss) DNA genome of ~5.5 kb that encodes a small noncoding RNA of 140 nucleotides known as bocavirus-encoded small RNA (BocaSR), in addition to viral proteins. Here, we determined the secondary structure of BocaSR in vivo by using DMS-MaPseq. Our findings reveal that BocaSR undergoes N6-methyladenosine (m6A) modification at multiple sites, which is critical for viral DNA replication in both dividing HEK293 cells and nondividing cells of the human airway epithelium. Mechanistically, we found that m6A-modified BocaSR serves as a mediator for recruiting Y-family DNA repair DNA polymerase (Pol) η and Pol κ likely through a direct interaction between BocaSR and the viral DNA replication origin at the right terminus of the viral genome. Thus, this report represents direct involvement of a viral small noncoding RNA in viral DNA replication through m6A modification.
Subject(s)
Adenosine , DNA Replication , DNA, Viral , DNA-Directed DNA Polymerase , RNA, Viral , Virus Replication , Humans , Adenosine/analogs & derivatives , Adenosine/metabolism , Virus Replication/genetics , DNA-Directed DNA Polymerase/metabolism , DNA-Directed DNA Polymerase/genetics , DNA, Viral/genetics , DNA, Viral/metabolism , HEK293 Cells , RNA, Viral/genetics , RNA, Viral/metabolism , Human bocavirus/genetics , Human bocavirus/metabolism , Genome, Viral/genetics , Parvoviridae Infections/virologyABSTRACT
Adeno-associated viruses (AAVs) package a single-stranded (ss) DNA genome of 4.7 kb in their capsid of ~20 nm in diameter. AAV replication requires co-infection of a helper virus, such as adenovirus. During the optimization of recombinant AAV production, a small viral nonstructural protein, membrane-associated accessory protein (MAAP), was identified. However, the function of the MAAP in the context of AAV infection remains unknown. Here, we investigated the expression strategy and function of the MAAP during infection of both AAV2 and AAV5 in human embryonic kidney (HEK)293 cells. We found that AAV2 MAAP2 and AAV5 MAAP5 are expressed from the capsid gene (cap)-transcribing mRNA spliced from the donor to the second splice site that encodes VP2 and VP3. Thus, this AAV cap gene transcribes a multicistronic mRNA that can be translated to four viral proteins, MAAP, VP2, AAP, and VP3 in order. In AAV2 infection, MAAP2 predominantly localized in the cytoplasm, alongside the capsid, near the nuclear and plasma membranes, but a fraction of MAAP2 exhibited nuclear localization. In AAV5 infection, MAAP5 revealed a distinct pattern, predominantly localizing within the nucleus. In the cells infected with an MAAP knockout mutant of AAV2 or AAV5, both viral DNA replication and virus replication increased, whereas virus egress decreased, and the decrease in virus egress can be restored by providing MAAP in trans. In summary, MAAP, a novel AAV nonstructural protein translated from a multicistronic viral cap mRNA, not only facilitates cellular egress of AAV but also likely negatively affects viral DNA replication during infection. IMPORTANCE: Recombinant adeno-associated virus (rAAV) has been used as a gene delivery vector in clinical gene therapy. In current gene therapies employing rAAV, a high dose of the vector is required. Consequently, there is a high demand for efficient and high-purity vector production systems. In this study, we demonstrated that membrane-associated accessory protein (MAAP), a small viral nonstructural protein, is translated from the same viral mRNA transcript encoding VP2 and VP3. In AAV-infected cells, apart from its prevalent expression in the cytoplasm with localization near the plasma and nuclear membranes, the MAAP also exhibits notable localization within the nucleus. During AAV infection, MAAP expression increases the cellular egress of progeny virions and decreases viral DNA replication and progeny virion production. Thus, the choice of MAAP expression has pros and cons during AAV infection, which could provide a guide to rAAV production.
Subject(s)
Dependovirus , Parvoviridae Infections , Viral Nonstructural Proteins , Humans , Capsid Proteins/genetics , Dependovirus/genetics , Dependovirus/metabolism , Dependovirus/physiology , HEK293 Cells , Parvoviridae Infections/virology , Viral Nonstructural Proteins/metabolism , Viral Nonstructural Proteins/genetics , Virus Replication , Genes, Viral/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Viral/genetics , RNA, Viral/metabolismABSTRACT
Virus-induced drought tolerance presents a fascinating facet of biotic-abiotic interaction in plants, yet its molecular intricacies remain unclear. Our study shows that cowpea mild mottle virus (CPMMV) infection enhances drought tolerance in common bean (Phaseolus vulgaris) plants through a virus-derived small interfering RNA (vsiRNA)-activated autophagy pathway. Specifically, a 21-bp vsiRNA originating from the CPMMV Triple Gene Block1 (TGB1) gene targeted the 5' untranslated region (UTR) of the host Teosinte branched 1, Cycloidea, Proliferating Cell Factor (TCP) transcription factor gene PvTCP2, independent of the known role of TGB1 as an RNA silencing suppressor. This targeting attenuated the expression of PvTCP2, which encodes a transcriptional repressor, and in turn upregulated the core autophagy-related gene (ATG) PvATG8c, leading to activated autophagy activity surpassing the level induced by drought or CPMMV infection alone. The downstream EARLY RESPONSIVE TO DEHYDRATION (ERD) effector PvERD15 is a homologue of Arabidopsis thaliana AtERD15, which positively regulates stomatal aperture. PvERD15 was degraded in PvATG8c-mediated autophagy. Therefore, we establish a TGB1-PvTCP2-PvATG8c-PvERD15 module as a trans-kingdom fine-tuning mechanism that contributes to virus-induced drought tolerance in plant-drought-virus interactions.
ABSTRACT
Metabolic reprogramming plays an important role in kidney cancer. We aim to investigate the causal effect of 249 metabolic biomarkers on kidney cancer from population-based data. This study extracts data from previous genome wide association studies with large sample size. The primary endpoint is random-effect inverse variance weighted (IVW). After completing 249 times of two-sample Mendelian randomization analysis, those significant metabolites are included for further sensitivity analysis. According to a strict Bonferrion-corrected level (P < 2e-04), we only find two metabolites that are causally associated with renal cancer. They are lactate (OR:3.25, 95% CI: 1.84-5.76, P = 5.08e-05) and phospholipids to total lipids ratio in large LDL (low density lipoprotein) (OR: 0.63, 95% CI: 0.50-0.80, P = 1.39e-04). The results are stable through all the sensitivity analysis. The results emphasize the central role of lactate in kidney tumorigenesis and provide novel insights into possible mechanism how phospholipids could affect kidney tumorigenesis.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Genome-Wide Association Study , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Carcinogenesis , Lactic Acid , Mendelian Randomization Analysis , Phospholipids , BiomarkersABSTRACT
COVID-19 caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2, (SARS-CoV-2) is a highly contagious disease known for its significant lung damage. Although the impact of the COVID-19 pandemic on our daily lives has been limited, the virus has not vanished entirely and continues to undergo mutations. This calls for a concentrated focus on the matter of SARS-CoV-2 immune evasion. Drawing on observations of immune escape mechanisms in other viruses, some scholars have proposed that liquid-liquid phase separation might play a crucial role in SARS-CoV-2's ability to evade the immune system. Within the structure of SARS-CoV-2, the nucleocapsid protein plays a pivotal role in RNA replication and transcription. Concurrently, this protein can engage in phase separation with RNA. A thorough examination of the phase separation related to the nucleocapsid protein may unveil the mechanism by which SARS-CoV-2 accomplishes immune evasion. Moreover, this analysis may provide valuable insights for future development of innovative antiviral drugs or vaccines.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Immune Evasion , Pandemics/prevention & control , Nucleocapsid ProteinsABSTRACT
BACKGROUND: The prognostic value of nutritional status in anaplastic thyroid carcinoma (ATC) remains unclear. The Prognostic Nutritional Index (PNI) is a reliable indicator of overall nutritional and immune status, and it has emerged as a significant prognostic factor in various malignancies. This study aimed to explore the utility of PNI in ATC. METHODS: We systematically reviewed ATC patients in our institute from January 2000 to June 2023 and categorized them into high and low PNI groups based on the median PNI value. Kaplan-Meier analysis and Cox regression were employed to assess the impact of PNI on overall survival, while ROC curve analysis evaluated the predictive value of PNI. Mimics software was used for three-dimensional reconstruction of pre- and post-immunotherapy tumor volumes, enabling the assessment of treatment response. RESULTS: A total of 77 ATC patients were included in this study. Low baseline PNI was associated with significantly shorter overall survival (1-year survival rate: 5.26% vs 30.77%; median survival time: 5.30 months vs 8.87 months). The 1-year, 2-year, and 3-year AUC values for PNI were 0.82, 0.79, and 0.77, respectively. In the multivariate analysis, both PNI and tumor size emerged as independent prognostic factors for patient overall survival. Among ATC patients receiving 2-3 cycles of immunotherapy, an increase in post-treatment PNI levels was positively correlated with a reduction in tumor volume. CONCLUSION: PNI is an independent predictor of overall survival and holds the potential to serve as a valuable indicator for assessing and predicting immunotherapy efficacy in ATC patients.
ABSTRACT
PURPOSE: The aim of this study was to investigate the association between myopia and longitudinal changes in peripapillary retinal nerve fiber layer (pRNFL) thickness in type 2 diabetic patients without diabetic retinopathy (DR). METHODS: A total of 1069 participants with a median follow-up time of 1.9 years were included in this study. The participants were categorized into four groups based on the presence of myopia (≤ -0.5 diopter [D]) and diabetes without DR, including a control group (n = 412), diabetes group (n = 416), myopia group (n = 115), and diabetes + myopia group (n = 126). Peripapillary average and sectoral RNFL measurements were obtained using 6 × 6 mm swept-source optical coherence tomography (SS-OCT) scans centered at the optic disc. The change rate of pRNFL, adjusted for age and sex, was calculated and compared among the four groups to investigate the impact of myopia and diabetes. RESULTS: The baseline estimated pRNFL thickness after adjustment for covariates was 113.7 µm, 116.2 µm, 108.0 µm, and 105.6 µm in the control, diabetes, myopia, and diabetes + myopia group, respectively (diabetes > control > myopia = diabetes + myopia, p < 0.001). The respective average pRNFL loss in the four groups was -0.48 µm/year, -1.11 µm/year, -1.23 µm/year, and -2.62 µm/year (all p < 0.01). The diabetes + myopia group exhibited a greater rate of average pRNFL reduction compared to the other groups (all p < 0.001). Multivariate analysis using a linear mixed-effects model showed that age, diabetes, axial length (AL), and baseline pRNFL thickness were significantly associated with the rate of average pRNFL reduction. CONCLUSIONS: The diabetes group showed a faster rate of average pRNFL thickness reduction compared to healthy controls, regardless of the presence of myopia. The average pRNFL thickness decreased more rapidly when diabetes and myopia were present simultaneously than in the individual diabetes or myopia group. Both diabetes and myopia were associated with accelerated pRNFL loss.
Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Retinopathy , Myopia , Nerve Fibers , Optic Disk , Retinal Ganglion Cells , Tomography, Optical Coherence , Humans , Male , Female , Tomography, Optical Coherence/methods , Nerve Fibers/pathology , Myopia/physiopathology , Myopia/complications , Myopia/diagnosis , Middle Aged , Retinal Ganglion Cells/pathology , Diabetes Mellitus, Type 2/complications , Optic Disk/pathology , Optic Disk/diagnostic imaging , Diabetic Retinopathy/diagnosis , Follow-Up Studies , Aged , Adult , Disease Progression , Visual Acuity/physiologyABSTRACT
BACKGROUND: Postoperative hypoparathyroidism (hypoPT) is a common complication following thyroid surgery. However, current research findings on the risk factors for post-thyroid surgery hypoPT are not entirely consistent, and the same risk factors may have different impacts on transient and permanent hypoPT. Therefore, there is a need for a comprehensive study to summarize and explore the risk factors for both transient and permanent hypoPT after thyroid surgery. MATERIALS AND METHODS: Two databases (PubMed and Embase) were searched from inception to 2024. The Newcastle-Ottawa Scale was used to rate study quality. Pooled odds ratios were used to calculate the relationship of each risk factor with transient and permanent hypoPT. Subgroup analyses were conducted for hypoPT with different definition-time (6 or 12 months). Publication bias was assessed using Begg's test and Egger's test. RESULTS: A total of 19 risk factors from the 93 studies were included in the analysis. Among them, sex and parathyroid autotransplantation were the most frequently reported risk factors. Meta-analysis demonstrated that sex (female vs. male), cN stage, central neck dissection, lateral neck dissection, extent of central neck dissection (bilateral vs. unilateral), surgery [total thyroidectomy (TT) vs. lobectomy], surgery type (TT vs. sub-TT), incidental parathyroidectomy, and pathology (cancer vs. benign) were significantly associated with transient and permanent hypoPT. Preoperative calcium and parathyroid autotransplantation were only identified as risk factors for transient hypoPT, while preoperative PTH was a protective factor. Additionally, node metastasis and parathyroid in specimen were associated with permanent hypoPT. CONCLUSION: The highest risk of hypoPT occurs in female thyroid cancer patients with lymph node metastasis undergoing TT combined with neck dissection. The key to preventing postoperative hypoPT lies in the selection of surgical approach and intraoperative protection.
Subject(s)
Hypoparathyroidism , Postoperative Complications , Thyroidectomy , Humans , Hypoparathyroidism/etiology , Hypoparathyroidism/epidemiology , Thyroidectomy/adverse effects , Risk Factors , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Female , Male , Sex FactorsABSTRACT
OBJECTIVE: To identify the causal role of sodium-glucose cotransporter 2 (SGLT2) inhibition on three urological cancers. METHODS: Six single nucleotide polymorphisms associated with the expression level of SLC5A2, a proxy for SGLT2 inhibition, from a recent publication were extracted. Three common urological cancers, including bladder cancer, prostate cancer and kidney cancer, were analysed. The main cohort of bladder cancer was derived from UK Biobank (1279 cases and 372,016 controls). The prostate cancer cohort was from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium (79,148 cases and 61,106 controls). The kidney cancer phenotype was from the UK Biobank cohort of 463,010 individuals (1114 cases and 461,896 controls). Primary and sensitivity analysis were performed to validate the results. In vitro analysis was also incorporated to validate the Mendelian randomisation results. RESULTS: In primary analysis, SGLT2 inhibition was associated with reduced risk of bladder cancer (OR: 0.98, 95% CI: 0.97-0.99) per unit lowering of HbA1c level. A protective association was also observed for prostate cancer with odds ratio = 0.31 (95% CI = 0.21-0.47). However, we did not discover a causal relationship between SGLT2 inhibition and kidney cancer (OR: 1.00, 95% CI: 0.99-1.00). Sensitivity analysis and in vitro validation did not support the causal role of SGLT2 inhibition in increasing cancer risk. CONCLUSIONS: We did not find any evidence that SGLT2 inhibition could increase the risk of the three cancers. Even in some analysis, SGLT2 inhibition tended to show protective effects on the three urological cancers.
Subject(s)
Kidney Neoplasms , Prostatic Neoplasms , Urinary Bladder Neoplasms , Urologic Neoplasms , Male , Humans , Sodium-Glucose Transporter 2/genetics , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/genetics , Urologic Neoplasms/epidemiology , Urologic Neoplasms/genetics , Urologic Neoplasms/complications , Urinary Bladder Neoplasms/epidemiology , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/complications , Kidney Neoplasms/epidemiology , Kidney Neoplasms/genetics , Kidney Neoplasms/complicationsABSTRACT
The noninvasive detection of pancreatic ductal adenocarcinoma (PDAC) remains an immense challenge. In this study, we proposed a robust, accurate, and noninvasive classifier, namely Multi-Omics Co-training Graph Convolutional Networks (MOCO-GCN). It achieved high accuracy (0.9 ± 0.06), F1 score (0.9± 0.07), and AUROC (0.89± 0.08), surpassing contemporary approaches. The performance of model was validated on an external cohort of German PDAC patients. Additionally, we discovered that the exposome may impact PDAC development through its complex interplay with gut microbiome by mediation analysis. For example, Fusobacterium hwasookii nucleatum, known for its ability to induce inflammatory responses, may serve as a mediator for the impact of rheumatoid arthritis on PDAC. Overall, our study sheds light on how exposome and microbiome in concert could contribute to PDAC development, and enable PDAC diagnosis with high fidelity and interpretability.
ABSTRACT
Developing highly sensitive and selective methods that incorporate specific recognition elements is crucial for detecting small molecules because of the limited availability of small molecule antibodies and the challenges in obtaining sensitive signals. In this study, a generalizable photoelectrochemical-colorimetric dual-mode sensing platform was constructed based on the synergistic effects of a molecularly imprinted polymer (MIP)-aptamer sandwich structure and nanoenzymes. The MIP functionalized peroxidase-like Fe3O4 (Fe3O4@MIPs) and alkaline phosphatase mimic Zr-MOF labeled aptamer (Zr-mof@Apt) were used as the recognition elements. By selectively accumulating dibutyl phthalate (DBP), a small molecule target model, on Fe3O4@MIPs, the formation of Zr-MOF@Apt-DBP- Fe3O4@MIPs sandwich structure was triggered. Fe3O4@MIPs oxidized TMB to form blue-colored oxTMB. However, upon selective accumulation of DBP, the catalytic activity of Fe3O4@MIPs was inhibited, resulting in a lighter color that was detectable by the colorimetric method. Additionally, Zr-mof@Apt effectively catalyzed the hydrolysis of L-Ascorbic acid 2-phosphate sesquimagnesium salt hydrate (AAPS), generating ascorbic acid (AA) that could neutralize the photogenerated holes to decrease the photocurrent signals for PEC sensing and reduce oxTMB for colorimetric testing. The dual-mode platform showed strong linearity for different concentrations of DBP from 1.0 pM to 10 µM (PEC) and 0.1 nM to 0.5 µM (colorimetry). The detection limits were 0.263 nM (PEC) and 30.1 nM (colorimetry) (S/N = 3), respectively. The integration of dual-signal measurement mode and sandwich recognition strategy provided a sensitive and accurate platform for the detection of small molecules.
Subject(s)
Biosensing Techniques , Molecularly Imprinted Polymers , Colorimetry/methods , Peroxidase/chemistry , PeroxidasesABSTRACT
BACKGROUND: The alteration of chromatin accessibility plays an important role in plant responses to abiotic stress. Carbon-based nanomaterials (CBNMs) have attracted increasing interest in agriculture due to their potential impact on crop productivity, showcasing effects on plant biological processes at transcriptional levels; however, their impact on chromatin accessibility remains unknown. RESULTS: This study found that fullerenol can penetrate the seed coat of pea to mitigate the reduction of seed germination caused by osmotic stress. RNA sequencing (RNA-seq) revealed that the application of fullerenol caused the high expression of genes related to oxidoreduction to return to a normal level. Assay for transposase accessible chromatin sequencing (ATAC-seq) confirmed that fullerenol application reduced the overall levels of chromatin accessibility of numerous genes, including those related to environmental signaling, transcriptional regulation, and metabolism. CONCLUSION: This study suggests that fullerenol alleviates osmotic stress on various fronts, encompassing antioxidant, transcriptional, and epigenetic levels. This advances knowledge of the working mechanism of this nanomaterial within plant cells. © 2024 Society of Chemical Industry.
Subject(s)
Chromatin Assembly and Disassembly , Fullerenes , Germination , Osmosis , Pisum sativum , Seeds , Seeds/chemistry , Seeds/metabolism , Seeds/growth & development , Germination/drug effects , Fullerenes/pharmacology , Pisum sativum/metabolism , Pisum sativum/genetics , Pisum sativum/chemistry , Chromatin Assembly and Disassembly/drug effects , Gene Expression Regulation, Plant/drug effects , Osmotic PressureABSTRACT
BACKGROUND: Hypopharyngeal and laryngeal squamous cell carcinoma (SCC) account for 25-30% of head and neck SCC. Total laryngectomy, while effective, compromises the quality of life. Immune checkpoint inhibitors such as Camrelizumab offer potential in laryngeal preservation. The study investigated Camrelizumab combined with TP regimen as a neoadjuvant therapy for laryngeal preservation in advanced hypopharyngeal and laryngeal SCC. METHODS: A retrospective study was conducted at Sun Yat-sen University Cancer Center on patients diagnosed with locally advanced SCC of the hypopharynx and larynx from October 1, 2019, to October 25, 2022. The efficacy of a first-line treatment combining Camrelizumab (200 mg) and TP regimen (Albumin-bound paclitaxel at 260 mg/m2 and Cisplatin at 60 mg/m2) was evaluated using RECIST 1.1 criteria. Outcomes included overall survival (OS), progression-free survival (PFS), laryngectomy-free survival (LFS), and response rates. RESULTS: Of the 71 included patients, the median age was 60.7 years. Post the first-line treatment, 90.1% demonstrated an overall response. The one-year and two-year OS rates were 91.5% and 84.3%, respectively. One-year and two-year PFS rates were 92.9% and 83.9%, respectively, with LFS at 85.6% and 73.2%. The initial T4 stage as significantly associated with reduced OS and LFS. Skin reaction was the predominant adverse event. CONCLUSION: The Camrelizumab-TP regimen demonstrated promising results for advanced hypopharyngeal/laryngeal SCC patients, exhibiting high response rates, OS, and LFS, positioning it as a potential primary option for laryngeal preservation. Further comprehensive, randomized controlled studies are imperative to validate these initial observations and elucidate the regimen's full clinical efficacy in optimizing laryngeal outcomes.
Subject(s)
Antibodies, Monoclonal, Humanized , Head and Neck Neoplasms , Larynx , Humans , Middle Aged , Neoadjuvant Therapy , Retrospective Studies , Hypopharynx , Quality of Life , Squamous Cell Carcinoma of Head and Neck/drug therapyABSTRACT
Bradyrhizobium is a genus of nitrogen-fixing bacteria, with some species producing nodules in leguminous plants. Investigations into Bradyrhizobium have recently revealed its substantial genetic resources and agricultural benefits, but a comprehensive survey of its genetic diversity and functional properties is lacking. Using a panel of various strains (N = 278), this study performed a comparative genomics analysis to anticipate genes linked with symbiotic nitrogen fixation. Bradyrhizobium's pan-genome consisted of 84,078 gene families, containing 824 core genes and 42,409 accessory genes. Core genes were mainly involved in crucial cell processes, while accessory genes served diverse functions, including nitrogen fixation and nodulation. Three distinct genetic profiles were identified based on the presence/absence of gene clusters related to nodulation, nitrogen fixation, and secretion systems. Most Bradyrhizobium strains from soil and non-leguminous plants lacked major nif/nod genes and were evolutionarily more closely related. These findings shed light on Bradyrhizobium's genetic features for symbiotic nitrogen fixation.
ABSTRACT
The Tibetan Plateau supplies water to nearly 2 billion people in Asia, but climate change poses threats to its aquatic microbial resources. Here, we construct the Tibetan Plateau Microbial Catalog by sequencing 498 metagenomes from six water ecosystems (saline lakes, freshwater lakes, rivers, hot springs, wetlands and glaciers). Our catalog expands knowledge of regional genomic diversity by presenting 32,355 metagenome-assembled genomes that de-replicated into 10,723 representative genome-based species, of which 88% were unannotated. The catalog contains nearly 300 million non-redundant gene clusters, of which 15% novel, and 73,864 biosynthetic gene clusters, of which 50% novel, thus expanding known functional diversity. Using these data, we investigate the Tibetan Plateau aquatic microbiome's biogeography along a distance of 2,500 km and >5 km in altitude. Microbial compositional similarity and the shared gene count with the Tibetan Plateau microbiome decline along with distance and altitude difference, suggesting a dispersal pattern. The Tibetan Plateau Microbial Catalog stands as a substantial repository for high-altitude aquatic microbiome resources, providing potential for discovering novel lineages and functions, and bridging knowledge gaps in microbiome biogeography.
Subject(s)
Microbiota , Humans , Tibet , Microbiota/genetics , Lakes , Rivers , WaterABSTRACT
Protein glycosylation is associated with the pathogenesis of various cancers. The utilization of certain glycans in cancer diagnosis models holds promise, yet their accuracy is not always guaranteed. Here, we investigated the utility of deep learning techniques, specifically random forests combined with transfer learning, in enhancing serum glycome's discriminative power for cancer diagnosis (including ovarian cancer, non-small cell lung cancer, gastric cancer, and esophageal cancer). We started with ovarian cancer and demonstrated that transfer learning can achieve superior performance in data-disadvantaged cohorts (AUROC >0.9), outperforming the approach of PLS-DA. We identified a serum glycan-biomarker panel including 18 serum N-glycans and 4 glycan derived traits, most of which were featured with sialylation. Furthermore, we validated advantage of the transfer learning scheme across other cancer groups. These findings highlighted the superiority of transfer learning in improving the performance of glycans-based cancer diagnosis model and identifying cancer biomarkers, providing a new high-fidelity cancer diagnosis venue.
ABSTRACT
BACKGROUND: Ovarian cancer (OC) is one of the most common gynecological tumors with high morbidity and mortality. Altered serum N-glycome has been observed in many diseases, while the association between serum protein N-glycosylation and OC progression remains unclear, particularly for the onset of carcinogenesis from benign neoplasms to cancer. METHODS: Herein, a mass spectrometry based high-throughput technique was applied to characterize serum N-glycome profile in individuals with healthy controls, benign neoplasms and different stages of OC. To elucidate the alterations of glycan features in OC progression, an orthogonal strategy with lectin-based ELISA was performed. RESULTS: It was observed that the initiation and development of OC was associated with increased high-mannosylationand agalactosylation, concurrently with decreased total sialylation of serum, each of which gained at least moderately accurate merits. The most important individual N-glycans in each glycan group was H7N2, H3N5 and H5N4S2F1, respectively. Notably, serum N-glycome could be used to accurately discriminate OC patients from benign cohorts, with a comparable or even higher diagnostic score compared to CA125 and HE4. Furthermore, bioinformatics analysis based discriminative model verified the diagnostic performance of serum N-glycome for OC in two independent sets. CONCLUSIONS: These findings demonstrated the great potential of serum N-glycome for OC diagnosis and precancerous lesion prediction, paving a new way for OC screening and monitoring.
Subject(s)
Ovarian Neoplasms , Precancerous Conditions , Humans , Female , Influenza A Virus, H7N2 Subtype , Biomarkers, Tumor , Ovarian Neoplasms/diagnosis , Polysaccharides/analysis , Precancerous Conditions/diagnosisABSTRACT
Objective To explore the therapeutic effect of "jian pi yi qi yang xue zhi tong" for treating bone metastasis of breast cancer and the clinical effect of improving pain symptoms. Methods A total of 80 patients with bone metastases from breast cancer were admitted. They were randomly divided into an observation group and a control group according to the random-number-table method. The control group was treated with zoledronic acid, whereas the observation group was treated with jian pi yi qi yang xue zhi tong prescriptions based on the control group. We compared the differences in the effects of different treatment plans on patients' pain symptoms, physical condition, and quality of life, as well as TNF-α, IL-6, and CRP levels. Results No significant difference was found in pain scores, physical condition scores, sleep quality scores, and quality of life scores, as well as CRP, IL-6, and TNF-α levels between the two groups of patients before treatment (all P > 0.05). At one, two, and four months after treatment, the pain scores of both groups of patients decreased, with the observation group having lower scores than the control group (P < 0.05). The total pain-relief rate of the observation group was higher than that of the control group (P < 0.05). After treatment, the sleep quality scores and the levels of CRP, IL-6, and TNF-α decreased, with the observation group having lower values than the control group (P < 0.05). The physical condition scores and the quality of life scores of both groups improved, with the observation group having higher values than the control group (P < 0.05). Conclusion In patients with bone metastases from breast cancer, oral treatment with jian pi yi qi yang xue zhi tong prescription has a significant effect. It substantially improves the pain symptoms, enhances the quality of sleep and life of patients, and reduces the levels of CRP, IL-6, and TNF-α.