Accurate etiological diagnosis of Mycoplasma hominis mediastinitis in immunocompetent patients using metagenomic next-generation sequencing: a case series and literature review.

Background: As a culture-independent method, metagenomic next-generation sequencing (mNGS) is widely used in microbiological diagnosis with advantages in identifying potential pathogens, guiding antibiotic therapy, and improving clinical prognosis, especially in culture-negative cases. Mycoplasma hominis (M. hominis) mediastinitis is a rare and severe disease for which etiological diagnosis is important but challenging. The application of mNGS in the etiological diagnosis of mediastinitis has seldom been studied. Methods: By searching the electronic medical history retrieval system with "Mycoplasma hominis" and "mediastinitis", seven patients diagnosed with M. hominis mediastinitis were reviewed in Zhongshan Hospital, Fudan University, Shanghai from 9 December 2020 to 14 February 2023. Microbiological cultures and mNGS were conducted for blood, abscess, and/or mediastinal fluid. Adjustment of the antibiotic therapy due to mNGS was assessed. A literature review was conducted in the PubMed database beginning in 1970 for M. hominis infection and mediastinitis. Results: For the seven patients, cultures of blood, abscess, and mediastinal fluid were negative whereas mNGS identified M. hominis in serum, abscess, and/or mediastinal fluid and was used to guide specific antibiotic therapy. The stringent mapped reads number of genera (SMRNG), stringent mapped reads number of species (SMRN), and coverage rate of M. hominis detection by mNGS were significantly higher in body fluid (abscess or mediastinal fluid) than in serum. All seven patients had underlying heart diseases and underwent previous cardiac surgery. The most common symptoms were fever and sternal pain. After detection of M. hominis, antibiotics were adjusted to quinolones or doxycycline except for one patient, whose diagnosis was clarified after death. Two patients died. Literature review since 1970 identified 30 cases of extra-genital infection caused by M. hominis. Including our seven new cases, 2 (5.4%) were neonates and 35 (94.6%) were adults. Thirty (81.1%) cases were postoperative infection and 15 (40.5%) had implanted devices. Five patients (13.5%) died. Conclusions: mNGS might be a promising technology in the detection of fastidious pathogens such as M. hominis. Accurate etiological diagnosis by mNGS could guide antibiotic therapy and facilitate clinical management.

KLF5-mediated pyroptosis of airway epithelial cells leads to airway inflammation in asthmatic mice through the miR-182-5p/TLR4 axis.

Asthma is viewed as an airway disease and an inflammatory condition. This study aims to reveal the role of Kruppel-like factor 5 (KLF5)-mediated pyroptosis of airway epithelial cells in airway inflammation in asthma. The asthmatic mouse model was established. The mice were infected with the lentivirus containing sh-KLF5, antagomiR-182-5p, and pc-Toll-like receptor 4 (TLR4). Airway hyperresponsiveness was measured, and the cells in bronchoalveolar lavage fluid (BALF) were sorted and counted. The expression levels of interleukin (IL)-4/IL-13/IL-6/IL-18/IL-1ß/NOD-like receptor family pyrin domain containing 3 (NLRP3)/N-gasdermin D (GSDMD-N)/cleaved caspase-1 were detected. The pathological changes in lung tissue were observed. The enrichment of KLF5 in the miR-182-5p promoter region was measured. The binding relationship among KLF5, miR-182-5p, and TLR4 were analyzed. KLF5 was highly expressed in asthmatic mice. Silencing KLF5 improved airway resistance and lung dynamic compliance, reduced the cells in BALF and the expression of IL-4/IL-13/IL-6/NLRP3/GSDMD-N/cleaved caspase-1/IL-18/IL-1ß, and alleviated the pathological changes. Mechanistically, KLF5 bonded to the miR-182-5p promoter to inhibit miR-182-5p expression, and miR-182-5p inhibited TLR4. Silencing miR-182-5p or TLR4 overexpression reversed the improvement of silencing KLF5 on airway inflammation and pyroptosis in asthmatic mice. In conclusion, KLF5 inhibited miR-182-5p to promote TLR4 expression, thus aggravating pyroptosis and airway inflammation in asthmatic mice.

IF1 Promotes Cellular Proliferation and Inhibits Oxidative Phosphorylation in Mouse Embryonic Fibroblasts under Normoxia and Hypoxia.

ATP synthase inhibitory factor subunit 1 (IF1) is an inhibitory subunit of mitochondrial ATP synthase, playing a crucial role in regulating mitochondrial respiration and energetics. It is well-established that IF1 interacts with the F1 sector of ATP synthase to inhibit the reversal rotation and, thus, ATP hydrolysis. Recent evidence supports that IF1 also inhibits forward rotation or the ATP synthesis activity. Adding to the complexity, IF1 may also facilitate mitophagy and cristae formation. The implications of these complex actions of IF1 for cellular function remain obscure. In the present study, we found that IF1 expression was markedly upregulated in hypoxic MEFs relative to normoxic MEFs. We investigate how IF1 affects cellular growth and function in cultured mouse embryonic fibroblasts derived from mouse lines with systemic IF1 overexpression and knockout under normoxia and hypoxia. Cell survival and proliferation analyses revealed that IF1 overexpression exerted limited effects on cellular viability but substantially increased proliferation under normoxia, whereas it facilitated both cellular viability and proliferation under hypoxia. The absence of IF1 may have a pro-survival effect but not a proliferative one in both normoxia and hypoxia. Cellular bioenergetic analyses revealed that IF1 suppressed cellular respiration when subjected to normoxia and was even more pronounced when subjected to hypoxia with increased mitochondrial ATP production. In contrast, IF1 knockout MEFs showed markedly increased cellular respiration under both normoxia and hypoxia with little change in mitochondrial ATP. Glycolytic stress assay revealed that IF1 overexpression modestly increased glycolysis in normoxia and hypoxia. Interestingly, the absence of IF1 in MEFs led to substantial increases in glycolysis. Therefore, we conclude that IF1 mainly inhibits cellular respiration and enhances cellular glycolysis to preserve mitochondrial ATP. On the other hand, IF1 deletion can significantly facilitate cellular respiration and glycolysis without leading to mitochondrial ATP deficit.

A modified QuEChERS-based UPLC-MS/MS method for rapid determination of multiple antibiotics and sedative residues in freshwater fish.

Antibiotics and sedatives are used in freshwater fish culture and transportation, and residue in freshwater fish pose potential risks to human health. Therefore, a throughput method was developed to detect antibiotic and sedative residues in fish, simultaneously quantifying 68 antibiotics and 9 sedatives in freshwater fish using a modified QuEChERS extraction method and UPLC-MS/MS. Matrix-matched calibrations demonstrated good correlation coefficients (R2 > 0.995), with a recovery range of 66.2-118.5%. The intra-day and inter-day relative standard deviation (RSD) were below 9.7% and 12.8%, respectively. The limits of detection (LOD) and quantification (LOQ) were 0.08-1.46 µg/kg and 0.25-4.86 µg/kg, respectively. 68.8% of analytes had weak matrix effects, and 13.0% had moderate matrix effects. In addition, diazepam and many types of antibiotics were detected in30 freshwater fish. The validation parameters were in agreement with the acceptable criteria of the Codex guidelines. The method was effective in analyzing antibiotic and sedative residues in freshwater fish.

[Advances in the research of transformation and stabilization of soil organic carbon from plant and microbe]. / æ¤ç‰©æºå’Œå¾®ç”Ÿç‰©æºåœŸå£¤æœ‰æœºç¢³è½¬åŒ–ä¸Žç¨³å®šç ”ç©¶è¿›å±•.

Soil organic carbon (SOC) is the core component of terrestrial carbon (C) sink. Exploring the transformation and stabilization mechanism of SOC is key to understand the function of terrestrial C sink which copes with climate change. The traditional perspective is that plant residues are the initial source of SOC. The new concept of "soil microbial C pump" emphasizes that the synthesized products of soil microbial assimilation are important contributors to the stable SOC. This provides a new insight to the sequestration mechanism of SOC. Due to the complex and variable decomposition process of plant residues and the high heterogeneity of microbial residues, the transformation and stabilization mechanism of plant residues and microbial residues into SOC is still unclear. We reviewed research progress in plant and microbial residues, and introduced the characterization methods of quantification and transformation of plant residues and microbial residues, and also summarized the new findings on the transformation of plant and microbial residues into SOC. We further discussed the contribution and driving factors of microbial and plant-derived C to SOC. Finally, we prospected the future development direction and research focus in this field. This review would provide the scientific reference for the research of soil C sequestration in terrestrial ecosystem.

Neuromorphic electro-stimulation based on atomically thin semiconductor for damage-free inflammation inhibition.

Inflammation, caused by accumulation of inflammatory cytokines from immunocytes, is prevalent in a variety of diseases. Electro-stimulation emerges as a promising candidate for inflammatory inhibition. Although electroacupuncture is free from surgical injury, it faces the challenges of imprecise pathways/current spikes, and insufficiently defined mechanisms, while non-optimal pathway or spike would require high current amplitude, which makes electro-stimulation usually accompanied by damage and complications. Here, we propose a neuromorphic electro-stimulation based on atomically thin semiconductor floating-gate memory interdigital circuit. Direct stimulation is achieved by wrapping sympathetic chain with flexible electrodes and floating-gate memory are programmable to fire bionic spikes, thus minimizing nerve damage. A substantial decrease (73.5%) in inflammatory cytokine IL-6 occurred, which also enabled better efficacy than commercial stimulator at record-low currents with damage-free to sympathetic neurons. Additionally, using transgenic mice, the anti-inflammation effect is determined by ß2 adrenergic signaling from myeloid cell lineage (monocytes/macrophages and granulocytes).

Results and analysis of examination doses for paediatric CT procedures based on a nationwide survey in China.

OBJECTIVE: To report the results of a dose survey conducted across 31 provinces in mainland China from 2017 to 2018 and to analyse the dose level to determine the national diagnostic reference levels (DRLs) for paediatric CT procedures. METHODS: At least ten patients for each age group (0- < 1, 1- < 5, 5- < 10, 10- < 15 years) and each procedure (head, chest and abdomen) for each CT scanner were selected from four to eight hospitals in each province. The dose information (CTDIvol and DLP) was collected from the HIS or RIS-PACS systems. The median values in each CT scanner were considered the representative dose values for the paediatric patients in CT scanning. The national DRLs were estimated based on the 75th percentile distribution of the median values. RESULTS: A total of 24,395 patients and 319 CT scanners were investigated across 262 hospitals. For paediatric CT scanning in 4 different age groups, the median (P50) and the 75th percentile (P75) of CTDIvol and DLP for each scanning procedure were calculated and reported. National DRLs were then proposed for each procedure and age group. CONCLUSION: The dose level of CT scanning for children in mainland China was reported for the first time. The DRLs for paediatric CT in the present study are similar to those in some Asian countries but higher than those in European countries. CLINICAL RELEVANCE STATEMENT: The paediatric CT is an extensively used tool in diagnosing paediatric disease; however, children are more sensitive to radiation. Establishing the diagnostic reference level of paediatric CT examination is necessary to reduce the dose of CT in children and promote the optimisation of medical exposure. KEY POINTS: • The DRLs for 3 paediatric CT procedures (head, chest and abdomen) and 4 age groups (0- < 1, 1- < 5, 5- < 10, 10- < 15 years) were proposed in mainland China first time. • The examination parameter and dose for children need to be further optimised in China, especially to lower the tube voltage in paediatric CT.

Interoceptive regulation of skeletal tissue homeostasis and repair.

Recent studies have determined that the nervous system can sense and respond to signals from skeletal tissue, a process known as skeletal interoception, which is crucial for maintaining bone homeostasis. The hypothalamus, located in the central nervous system (CNS), plays a key role in processing interoceptive signals and regulating bone homeostasis through the autonomic nervous system, neuropeptide release, and neuroendocrine mechanisms. These mechanisms control the differentiation of mesenchymal stem cells into osteoblasts (OBs), the activation of osteoclasts (OCs), and the functional activities of bone cells. Sensory nerves extensively innervate skeletal tissues, facilitating the transmission of interoceptive signals to the CNS. This review provides a comprehensive overview of current research on the generation and coordination of skeletal interoceptive signals by the CNS to maintain bone homeostasis and their potential role in pathological conditions. The findings expand our understanding of intersystem communication in bone biology and may have implications for developing novel therapeutic strategies for bone diseases.

Urinary Metabolomic Analysis of Prostate Cancer by UPLC-FTMS and UPLC-Ion Trap MSn.

Accumulative evidence suggests metabolic disorders correlate with prostate cancer. Metabolic profiling of urine allows the measurement of numerous metabolites simultaneously. This study set up a metabolomic platform consisting of UPLC-FTMS and UPLC-ion trap MSn for urine metabolome analysis. The platform improved retention time, mass accuracy, and signal stability. Additionally, the product ion spectrum obtained from ion trap MSn facilitated structure elucidation of candidate metabolites, especially when authentic standards were not available. Urine samples from six hernia patients and six BPH patients were used for the initial establishment of the analytic platform. This platform was further employed to analyze the urine samples of 27 PCa and 49 BPH patients. Choosing the upper and lower 16% of metabolites, 258 metabolite candidates were selected. Twenty-four of them with AUC values larger than 0.65 were further selected. Eighteen of the twenty-four features can be matched in METLIN and HMDB. Eleven of the eighteen features can be interpreted by MSn experiments. They were used for the combination achieving the best differential power. Finally, four metabolites were combined to reach the AUC value of 0.842 (CI 95, 0.7559 to 0.9279). This study demonstrates the urinary metabolomic analysis of prostate cancer and sheds light on future research.

Cytokine and chemokine map of peripheral specific immune cell subsets in Parkinson's disease.

Peripheral immune cells play a vital role in the development of Parkinson's disease (PD). However, their cytokine and chemokine secretion functions remain unclear. Therefore, we aimed to explore the cytokine and chemokine secretion functions of specific immune cell subtypes in drug-naïve patients with PD at different ages of onset. We included 10 early-onset and 10 late-onset patients with PD and age-matched healthy controls (HCs). We used mass cytometry to select specific immune cell subsets and evaluate intracellular cytokine and chemokine expression. Statistical tests included t-tests, analysis of variance, bivariate correlation analysis, and linear regression analysis. Compared with HCs, patients with PD exhibited significantly decreased intracellular pro-inflammatory cytokines and chemokines in selected clusters (e.g., tumor necrosis factor (TNF)-α, interleukin (IL)-8, IL-1ß, and CC-chemokine ligand (CCL)17). Specific cytokines and cell clusters were associated with clinical symptoms. TNF-α played an important role in cognitive impairment. Intracellular TNF-α levels in the naïve CD8+ T-cell cluster C16 (CD57- naïve CD8+ T) and natural killer (NK) cell cluster C32 (CD57- CD28- NK) were negatively correlated with Montreal Cognitive Assessment scores. The C16 cluster affected cognitive function and motor symptoms. Increased TNF-α and decreased interferon-γ expression in C16 correlated with increased Unified Parkinson's Disease Rating Scale III scores in patients with PD. In summary, we developed a more detailed cytokine and chemokine map of peripheral specific CD8+ T cell and NK cell subsets, which revealed disrupted secretory function in patients with PD and provided unique clues for further mechanistic exploration.

Nuclear DJ-1 Regulates DNA Damage Repair via the Regulation of PARP1 Activity.

DNA damage and defective DNA repair are extensively linked to neurodegeneration in Parkinson's disease (PD), but the underlying molecular mechanisms remain poorly understood. Here, we determined that the PD-associated protein DJ-1 plays an essential role in modulating DNA double-strand break (DSB) repair. Specifically, DJ-1 is a DNA damage response (DDR) protein that can be recruited to DNA damage sites, where it promotes DSB repair through both homologous recombination and nonhomologous end joining. Mechanistically, DJ-1 interacts directly with PARP1, a nuclear enzyme essential for genomic stability, and stimulates its enzymatic activity during DNA repair. Importantly, cells from PD patients with the DJ-1 mutation also have defective PARP1 activity and impaired repair of DSBs. In summary, our findings uncover a novel function of nuclear DJ-1 in DNA repair and genome stability maintenance, and suggest that defective DNA repair may contribute to the pathogenesis of PD linked to DJ-1 mutations.

Crop-Weed Introgression Plays Critical Roles in Genetic Differentiation and Diversity of Weedy Rice: A Case Study of Human-Influenced Weed Evolution.

As an important driving force, introgression plays an essential role in shaping the evolution of plant species. However, knowledge concerning how introgression affects plant evolution in agroecosystems with strong human influences is still limited. To generate such knowledge, we used InDel (insertion/deletion) molecular fingerprints to determine the level of introgression from japonica rice cultivars into the indica type of weedy rice. We also analyzed the impact of crop-to-weed introgression on the genetic differentiation and diversity of weedy rice, using InDel (insertion/deletion) and SSR (simple sequence repeat) molecular fingerprints. Results based on the STRUCTURE analysis indicated an evident admixture of some weedy rice samples with indica and japonica components, suggesting different levels of introgression from japonica rice cultivars to the indica type of weedy rice. The principal coordinate analyses indicated indica-japonica genetic differentiation among weedy rice samples, which was positively correlated with the introgression of japonica-specific alleles from the rice cultivars. In addition, increased crop-to-weed introgression formed a parabola pattern of dynamic genetic diversity in weedy rice. Our findings based on this case study provide evidence that human activities, such as the frequent change in crop varieties, can strongly influence weed evolution by altering genetic differentiation and genetic diversity through crop-weed introgression in agroecosystems.

DNA Damage-Mediated Neurotoxicity in Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease around the world; however, its pathogenesis remains unclear so far. Recent advances have shown that DNA damage and repair deficiency play an important role in the pathophysiology of PD. There is growing evidence suggesting that DNA damage is involved in the propagation of cellular damage in PD, leading to neuropathology under different conditions. Here, we reviewed the current work on DNA damage repair in PD. First, we outlined the evidence and causes of DNA damage in PD. Second, we described the potential pathways by which DNA damage mediates neurotoxicity in PD and discussed the precise mechanisms that drive these processes by DNA damage. In addition, we looked ahead to the potential interventions targeting DNA damage and repair. Finally, based on the current status of research, key problems that need to be addressed in future research were proposed.

Parkin regulates microglial NLRP3 and represses neurodegeneration in Parkinson's disease.

Microglial hyperactivation of the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome contributes to the pathogenesis of Parkinson's disease (PD). Recently, neuronally expressed NLRP3 was demonstrated to be a Parkin polyubiquitination substrate and a driver of neurodegeneration in PD. However, the role of Parkin in NLRP3 inflammasome activation in microglia remains unclear. Thus, we aimed to investigate whether Parkin regulates NLRP3 in microglia. We investigated the role of Parkin in NLRP3 inflammasome activation through the overexpression of Parkin in BV2 microglial cells and knockout of Parkin in primary microglia after lipopolysaccharide (LPS) treatment. Immunoprecipitation experiments were conducted to quantify the ubiquitination levels of NLRP3 under various conditions and to assess the interaction between Parkin and NLRP3. In vivo experiments were conducted by administering intraperitoneal injections of LPS in wild-type and Parkin knockout mice. The Rotarod test, pole test, and open field test were performed to evaluate motor functions. Immunofluorescence was performed for pathological detection of key proteins. Overexpression of Parkin mediated NLRP3 degradation via K48-linked polyubiquitination in microglia. The loss of Parkin activity in LPS-induced mice resulted in excessive microglial NLRP3 inflammasome assembly, facilitating motor impairment, and dopaminergic neuron loss in the substantia nigra. Accelerating Parkin-induced NLRP3 degradation by administration of a heat shock protein (HSP90) inhibitor reduced the inflammatory response. Parkin regulates microglial NLRP3 inflammasome activation through polyubiquitination and alleviates neurodegeneration in PD. These results suggest that targeting Parkin-mediated microglial NLRP3 inflammasome activity could be a potential therapeutic strategy for PD.

Sustained Release of Dicumarol via Novel Grafted Polymer in Electrospun Nanofiber Membrane for Treatment of Peritendinous Adhesion.

The prevention and treatment of post-traumatic peritendinous adhesion (PA) have always been a great difficulty for orthopedic surgeons. Current treatments include resecting surgery, non-steroidal anti-inflammatory drugs (NSAIDs) usage and implantable membranes, often target single disease pathogenic processes, resulting in unfavorable therapeutic outcomes. Here a polylactic acid (PLA)-dicumarol conjugates-electrospun nanofiber membrane (ENM) (PCD) is generated, which can achieve spatial accuracy and temporal sustainability in drug release. It is further demonstrated that PCD possesses a significantly higher and more sustainable drug release profile than traditional drug-loading ENM. By providing a physical barrier and continuous releasing of dicumarol, PCD implantation significantly reduces tissue adhesion by 25%, decreases fibroblasts activity and inhibits key fibrogenic cytokine transforming growth factor beta (TGFß) production by 30%, and improves the biomechanical tendon property by 14.69%. Mechanistically, PCD potently inhibits the connexin43 (Cx43) and thereby tunes down the fibroblastic TGFß/Smad3 signaling pathway. Thus, this approach leverages the anti-adhesion effect of dicumarol and drug release properties of grafted copolymer ENM by esters to provide a promising therapeutic strategy for patients who suffer from PA.

X-linked Charcot-Marie-Tooth disease after SARS-CoV-2 vaccination mimicked stroke-like episodes: A case report.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations have been administered worldwide, with occasional reports of associated neurological complications. Specifically, the impact of vaccinations on individuals with X-linked Charcot-Marie-Tooth disease type 1 (CMTX1) is unclear. Patients with CMTX1 can have stroke-like episodes with posterior reversible encephalopathy syndrome on magnetic resonance imaging (MRI), although this is rare. CASE SUMMARY: A 39-year-old man was admitted with episodic aphasia and dysphagia for 2 d. He received SARS-CoV-2 vaccination 39 d before admission. Physical examination showed pes cavus and reduced tendon reflexes. Brain MRI showed bilateral, symmetrical, restricted diffusion with T2 hyperintensities in the cerebral hemispheres. Nerve conduction studies revealed peripheral nerve damage. He was diagnosed with Charcot-Marie-Tooth disease, and a hemizygous mutation in the GJB1 gene on the X chromosome, known to be pathogenic for CMTX1, was identified. Initially, we suspected transient ischemic attack or demyelinating leukoencephalopathy. We initiated treatment with antithrombotic therapy and immunotherapy. At 1.5 mo after discharge, brain MRI showed complete resolution of lesions, with no recurrence. CONCLUSION: SARS-CoV-2 vaccination could be a predisposing factor for CMTX1 and trigger a sudden presentation.

Elevated serum anti-Saccharomyces cerevisiae antibody accompanied by gut mycobiota dysbiosis as a biomarker of diagnosis in patients with de novo Parkinson disease.

BACKGROUND AND PURPOSE: Intestinal inflammation and gut microbiota dysbiosis contribute to Parkinson disease (PD) pathogenesis, and growing evidence suggests associations between inflammatory bowel diseases (IBD) and PD. Considered as markers of chronic gastrointestinal inflammation, elevated serum anti-Saccharomyces cerevisiae antibody (ASCA) levels, against certain gut fungal components, are related to IBD, but their effect on PD is yet to be investigated. METHODS: Serum ASCA IgG and IgA levels were measured using an enzyme-linked immunosorbent assay, and the gut mycobiota communities were investigated using ITS2 sequencing and analyzed using the Qiime pipeline. RESULTS: The study included 393 subjects (148 healthy controls [HCs], 140 with PD, and 105 with essential tremor [ET]). Both serum ASCA IgG and IgA levels were significantly higher in the PD group than in the ET and HC groups. Combining serum ASCA levels and the occurrence of constipation could discriminate patients with PD from controls (area under the curve [AUC] = 0.81, 95% confidence interval [CI] = 0.76-0.86) and from patients with ET (AUC = 0.85, 95% CI = 0.79-0.89). Furthermore, the composition of the gut fungal community differed between the PD and HC groups. The relative abundances of Saccharomyces cerevisiae, Aspergillus, Candida solani, Aspergillus flavus, ASV601_Fungi, ASV866_Fungi, and ASV755_Fungi were significantly higher in the PD group, and enriched Malassezia restricta was found in the HC group. CONCLUSIONS: Our study identified elevated serum ASCA levels and enriched gut Saccharomyces cerevisiae in de novo PD.

Pharmacogenomics-a New Frontier for Individualized Treatment of Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease with a significant public health burden. It is characterized by the gradual degeneration of dopamine neurons in the central nervous system. Although symptomatic pharmacological management remains the primary therapeutic method for PD, clinical experience reveals significant inter-individual heterogeneity in treatment effectiveness and adverse medication responses. The mechanisms behind the observed interindividual variability may be elucidated by investigating the role of genetic variation in human-to-human variances in medication responses and adverse effects. OBJECTIVE: This review aims to explore the impact of gene polymorphism on the efficacy of antiparkinsonian drugs. The identification of factors associated with treatment effectiveness variability might assist the creation of a more tailored pharmacological therapy with higher efficacy, fewer side outcomes, and cheaper costs. METHODS: In this review, we conducted a thorough search in databases such as PubMed, Web of Science, and Google Scholar, and critically examined current discoveries on Parkinson's disease pharmacogenetics. The ethnicity of the individuals, research methodologies, and potential bias of these studies were thoroughly compared, with the primary focus on consistent conclusions. RESULTS: This review provides a summary of the existing data on PD pharmacogenetics, identifies its limitations, and offers insights that may be beneficial for future research. Previous studies have investigated the impact of gene polymorphism on the effectiveness and adverse effects of levodopa. The trendiest genes are the COMT gene, DAT gene, and DRD2 gene. However, limited study on other anti-Parkinson's drugs has been conducted. CONCLUSION: Therefore, In order to develop an individualized precision treatment for PD, it is an inevitable trend to carry out multi-center, prospective, randomized controlled clinical trials of PD pharmacogenomics covering common clinical anti-PD drugs in large, homogeneous cohorts.

Impact of cognition-related single nucleotide polymorphisms on brain imaging phenotype in Parkinson's disease.

Multiple single nucleotide polymorphisms may contribute to cognitive decline in Parkinson's disease. However, the mechanism by which these single nucleotide polymorphisms modify brain imaging phenotype remains unclear. The aim of this study was to investigate the potential effects of multiple single nucleotide polymorphisms on brain imaging phenotype in Parkinson's disease. Forty-eight Parkinson's disease patients and 39 matched healthy controls underwent genotyping and 7T magnetic resonance imaging. A cognitive-weighted polygenic risk score model was designed, in which the effect sizes were determined individually for 36 single nucleotide polymorphisms. The correlations between polygenic risk score, neuroimaging features, and clinical data were analyzed. Furthermore, individual single nucleotide polymorphism analysis was performed to explore the main effects of genotypes and their interactive effects with Parkinson's disease diagnosis. We found that, in Parkinson's disease, the polygenic risk score was correlated with the neural activity of the hippocampus, parahippocampus, and fusiform gyrus, and with hippocampal-prefrontal and fusiform-temporal connectivity, as well as with gray matter alterations in the orbitofrontal cortex. In addition, we found that single nucleotide polymorphisms in α-synuclein (SNCA) were associated with white matter microstructural changes in the superior corona radiata, corpus callosum, and external capsule. A single nucleotide polymorphism in catechol-O-methyltransferase was associated with the neural activities of the lingual, fusiform, and occipital gyri, which are involved in visual cognitive dysfunction. Furthermore, DRD3 was associated with frontal and temporal lobe function and structure. In conclusion, imaging genetics is useful for providing a better understanding of the genetic pathways involved in the pathophysiologic processes underlying Parkinson's disease. This study provides evidence of an association between genetic factors, cognitive functions, and multi-modality neuroimaging biomarkers in Parkinson's disease.

Reduced Carbon Dioxide by Overexpressing EPSPS Transgene in Arabidopsis and Rice: Implications in Carbon Neutrality through Genetically Engineered Plants.

With the increasing challenges of climate change caused by global warming, the effective reduction of carbon dioxide (CO2) becomes an urgent environmental issue for the sustainable development of human society. Previous reports indicated increased biomass in genetically engineered (GE) Arabidopsis and rice overexpressing the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene, suggesting the possibility of consuming more carbon by GE plants. However, whether overexpressing the EPSPS gene in GE plants consumes more CO2 remains a question. To address this question, we measured expression of the EPSPS gene, intercellular CO2 concentration, photosynthetic ratios, and gene expression (RNA-seq and RT-qPCR) in GE (overexpression) and non-GE (normal expression) Arabidopsis and rice plants. Results showed substantially increased EPSPS expression accompanied with CO2 consumption in the GE Arabidopsis and rice plants. Furthermore, overexpressing the EPSPS gene affected carbon-fixation related biological pathways. We also confirmed significant upregulation of four key carbon-fixation associated genes, in addition to increased photosynthetic ratios, in all GE plants. Our finding of significantly enhanced carbon fixation in GE plants overexpressing the EPSPS transgene provides a novel strategy to reduce global CO2 for carbon neutrality by genetic engineering of plant species, in addition to increased plant production by enhanced photosynthesis.