Association of pro-inflammatory diet with increased risk of gallstone disease: a cross-sectional study of NHANES January 2017-March 2020.

Background and aim: Gallstone disease (GSD) is a major public health problem worldwide. The dietary inflammatory index (DII) and the energy-adjusted DII (E-DII) have been used to describe dietary inflammatory potential. The current study sought to investigate the pro-inflammatory role of diet on GSD among outpatients in the United States. Methods: Cross-sectional data from 7,334 individuals older than 20 years who participated in the National Health and Nutrition Examination Survey (NHANES) from January 2017 to March 2020 were obtained. The relationship between GSD and DII was assessed using self-reported data. An association between DII and the risk of GSD was determined using sample-weighted logistic regression and restricted cubic splines (RCS). Subgroup analyzes were conducted to assess the interaction between DII and related factors. Sensitivity analysis was further used to confirm the stability of the relationship. To control for the effect of total energy intake, E-DII was calculated and analyzed. Results: A total of 10.5% of the study participants had GSD. The DII ranged from -5.52 to 5.51, and the median DII was significantly higher for participants with GSD than those without (1.68 vs. 1.23, p < 0.001). There was a significant and stable positive relationship between DII and GSD in adjusted models (OR 1.10, 95% CI 1.00-1.20). In the fully adjusted model, subjects with DII scores in the highest tertile were more likely to have GSD than those in the lowest tertile (OR 1.52, 95% CI 1.19-1.93). An apparent dose-response association between DII and GSD was detected. The association between E-DII and GSD remained stable. Conclusion: Higher DII/E-DII scores linked to the intake of a pro-inflammatory diet were positively associated with a higher risk of GSD. These findings suggest that pro-inflammatory dietary patterns can promote the formation of gallstones.

Transcription factor PbNAC71 regulates xylem and vessel development to control plant height.

Dwarfism is an important agronomic trait in fruit breeding programs. However, the germplasm resources required to generate dwarf pear (Pyrus spp.) varieties are limited. Moreover, the mechanisms underlying dwarfism remain unclear. In this study, "Yunnan" quince (Cydonia oblonga Mill.) had a dwarfing effect on "Zaosu" pear. Additionally, the dwarfism-related NAC transcription factor gene PbNAC71 was isolated from pear trees comprising "Zaosu" (scion) grafted onto "Yunnan" quince (rootstock). Transgenic Nicotiana benthamiana and pear OHF-333 (Pyrus communis) plants overexpressing PbNAC71 exhibited dwarfism, with a substantially smaller xylem and vessel area relative to the wild-type controls. Yeast one-hybrid, dual-luciferase, chromatin immunoprecipitation-qPCR, and electrophoretic mobility shift assays indicated that PbNAC71 downregulates PbWalls are thin 1 expression by binding to NAC-binding elements in its promoter. Yeast two-hybrid assays showed that PbNAC71 interacts with the E3 ubiquitin ligase PbRING finger protein 217 (PbRNF217). Furthermore, PbRNF217 promotes the ubiquitin-mediated degradation of PbNAC71 by the 26S proteasome, thereby regulating plant height as well as xylem and vessel development. Our findings reveal a mechanism underlying pear dwarfism and expand our understanding of the molecular basis of dwarfism in woody plants.

Clinical application of metagenomic next-generation sequencing in patients with different organ system infection: A retrospective observational study.

Microbiological identification is essential for appropriate treatment, but conventional methods are time-consuming and have a low sensitivity. In contrast, metagenomic next-generation sequencing (mNGS) is a culture-free and hypothesis-free technique that can detect a wide array of potential pathogens. This study aimed to reveal the overall diagnostic value of mNGS for infectious diseases of different organ systems and compare the sensitivity and specificity of mNGS with conventional methods. In a retrospective cohort study, 94 patients with mNGS results were enrolled, and clinical data were recorded and analyzed to compare the positive rate of mNGS with traditional methods including as smears, serological tests, and traditional PCR, etc. In this study, mNGS and culture were both positive in 12.77% cases and were both negative in 23.4% cases. There were positive results in 56 cases (54.26%) only by mNGS and 4 cases (4.26%) were positive only by culture. There were significant differences in sensitivity of pathogen detection between of ID and NID group for mNGS (χ2 = 10.461, P = .001)and conventional methods(χ2 = 7.963, P = .005). The positive predictive values and negative predictive values of diagnosing infectious disease by mNGS were 94.12% and 30.77%, respectively. mNGS increased the sensitivity rate by approximately 53.66% compared with that of culture (78.05% vs24.39%; χ2 = 47.248, P < .001) and decreased the specificity rate by 12.5% compared with that of culture (66.67% vs 100.0%; χ2 = 4.8, P = .028). mNGS can identify emerging or rare pathogen and further guide treatment regimens. mNGS has advantages in identifying overall pathogens and bacteria, however, there was no obvious advantage in identifying fungi, virus and tuberculosis. mNGS has higher specificity than conventional methods in identifying pathogens and advantages in detecting emerging or rare pathogens.

OPEs-ID: A software for non-targeted screening of organophosphate esters based on liquid chromatography-high-resolution mass spectrometry.

Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers, presenting a potential threat to the environment and human health. To date, no automatic software exists for the nontargeted screening of OPEs. In this study, OPEs-ID, a user-friendly software, was developed for the identification of OPEs using liquid chromatography-high-resolution mass spectrometry. The main workflow of OPEs-ID included fragments-dependent precursor ion screening, elemental composition determination, extracted ion chromatograms (EIC) comparison, and molecular structure identification via MetFrag strategy. A mixture of 17 OPE standards was identified with an identification rate of 100% by OPEs-ID. OPEs-ID demonstrated a rate of 94.1% for correctly ranking within the top 1 candidate in a local database (41.2% in PubChem) for the 17 OPE standards, which remarkably improved the identification when compared to conventional in silico fragmentation algorithms. Using a pooled airborne fine particle sample (PM2.5), OPEs-ID could automatically retrieve 22 valid molecules with structure candidates. The detection frequencies of 9 newly identified OPEs were between 13% and 100% in the 32 PM2.5 samples. Their semi-quantification concentrations were comparable to those of some traditional OPEs. Overall, OPEs-ID offers a powerful tool to significantly enrich our understanding of the OPEs present in the environment.

Sorption of representative organic contaminants on microplastics: Effects of chemical physicochemical properties, particle size, and biofilm presence.

Microplastic pollution has attracted mounting concerns worldwide. Microplastics may concentrate organic and metallic contaminants; thus, affecting their transport, fate and organismal exposure. To better understand organic contaminant-microplastic interactions, our study explored the sorption of selected polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), α-hexabromocyclododecane (α-HBCDD), and organophosphate flame retardants (OPFRs) on high-density polyethylene (HDPE) and polyvinylchloride (PVC) microplastics under saline conditions. Sorption isotherms determined varied between chemicals and between HDPE and PVC microplastics. Log Freundlich sorption coefficients (Log KF) for the targeted chemicals ranged from 2.01 to 5.27 L kg-1 for HDPE, but were significantly lower for PVC, i.e., ranging from Log KF data (2.84 - 8.58 L kg-1). Significant correlations between chemicals' Log KF and Log Kow (octanol-water partition coefficient) indicate that chemical-dependent sorption was largely influenced by their hydrophobicity. Sorption was evaluated using three size classes (< 53, 53 - 300, and 300 - 1000 µm) of lab-fragmented microplastics. Particle size did not significantly affect sorption isotherms, but influenced the time to reach equilibrium and the predicted maximum sorption, likely related to microplastic surface areas. The presence of biofilms on HDPE particles significantly enhanced contaminant sorption capacity, indicating more complex sorption dynamics in the chemical-biofilm-microplastic system. Our findings offer new insights into the chemical-microplastic interactions in marine environment.

Severe skin and subcutaneous pythiosis in China: Metagenomic identification and characterization of Pythium insidiosum.

Pythium insidiosum is a rare fungus-like pathogen that is known to cause pythiosis in mammals with high morbidity and mortality. Identification of the pathogen is essential for timely treatment and rational use of antibiotics. However, Pythium insidiosum is difficult to detect via conventional microbiological tests. The current gold standard is polymerase chain reaction, which is lacking in most hospitals since human pythiosis is rare in China. In this study, we used metagenomic Next-Generation Sequencing and identified Pythium insidiosum in a 56-year-old Chinese male who was hospitalized due to severe edema in the right lower limb with scattered darkening indurations. The patient had a history of cirrhosis and occupational exposure to swamp water. Serological level of immune biomarkers indicated immunodeficiency, and Proteinase 3-Anti-Neutrophil Cytoplasmic Antibody was positive. Surgical incision of the lesions revealed radiating and reticular cutaneous ulcers. Microbial infections were suspected but conventional tests failed to discover the etiology. Empirical use of penicillin, vancomycin, and ceftriaxone had no effect. As a result, the peripheral blood and tissue biopsies were sent for metagenomic Next-Generation Sequencing, which reported Pythium insidiosum. This finding was corroborated by pathological staining, whole-genome sequencing, and internal transcribed spacer sequencing. Notably, antifungal treatment was ineffective, but the patient responded well to oral trimethoprim-sulfamethoxazole, which may be due to the folp gene found in Pythium insidiosum genome. Our study prompts future studies to determine the optimal treatment of skin pythiosis.

DLC1 inhibits colon adenocarcinoma cell migration by promoting secretion of the neurotrophic factor MANF.

DLC1 (deleted in liver cancer-1) is downregulated or deleted in colorectal cancer (CRC) tissues and functions as a potent tumor suppressor, but the underlying molecular mechanism remains elusive. We found that the conditioned medium (CM) collected from DLC1-overexpressed SW1116 cells inhibited the migration of colon adenocarcinoma cells HCT116 and SW1116, but had no effect on proliferation, which suggested DLC1-mediated secretory components containing a specific inhibitor for colon adenocarcinoma cell migration. Analysis by mass spectrometry identified mesencephalic astrocyte-derived neurotrophic factor (MANF) as a candidate. More importantly, exogenous MANF significantly inhibited the migration of colon adenocarcinoma cells HCT116 and SW1116, but did not affect proliferation. Mechanistically, DLC1 reduced the retention of MANF in ER by competing the interaction between MANF and GRP78. Taken together, these data provided new insights into the suppressive effects of DLC1 on CRC, and revealed the potential of MANF in the treatment of CRC.

ScCBF1 plays a stronger role in cold, salt and drought tolerance than StCBF1 in potato (Solanum tuberosum).

Solanum tuberosum (St) and Solanum commersonii (Sc) are two potato varieties with different freezing tolerance. Among them, St is a freezing-sensitive variety and. Sc is a cold-resistant wild potato. CBF/DREB family members mainly function in response to freezing stress. In order to explore the different roles of St C-Repeat Binding Factor1 (StCBF1) and Sc C-Repeat Binding Factor1 (ScCBF1) in potato plants (Solanum tuberosum) under stress conditions, two kinds of potato lines were obtained with ScCBF1 and StCBF1 overexpressing respectively. Phenotypes analysis showed that both overexpressing ScCBF1 and StCBF1 caused smaller leaves, and reduced tuber yield. While the limited phenotypes of StCBF1 lines were more severe than that of ScCBF lines. After freezing treatment, StCBF1 over expression plants grown better than WT plants and worse than ScCBF1 over expression plants. Specifically, compared with wild-type lines, overexpressing ScCBF1 could up-regulate fatty acid desaturase genes, key enzyme of Calvin cycle genes, and antioxidant enzyme genes. Both ScCBF1 and StCBF1 lines showed higher PSII activity, thus maintaining a higher photosynthetic rate under cold stress. In addition, we also found that overexpression ScCBF1 and StCBF1 could also enhance the drought and salt tolerance in potato. In summary, ScCBF1 plays a stronger role in cold, salt, and drought tolerance than StCBF1 in potato (Solanum tuberosum).

Swimming Impedes Intestinal Microbiota and Lipid Metabolites of Tumorigenesis in Colitis-Associated Cancer.

Background: Accumulating data support that regular physical activity potentially inhibits chronic colitis, a risk factor for colitis-associated cancer (CAC). However, possible effects of physical activity on CAC and the underlying mechanisms remain poorly understood. Methods: A pretreatment of swimming on azoxymethane/dextran sodium sulfate (AOM/DSS)-induced CAC mice was implemented to determine its protective effect. Inflammation and tumorigenesis were assessed using colorectums from C57BL/6 mice. In order to determine how swimming alters colonic lipid metabolism and gene expression, a comparative analysis was conducted. Meanwhile, alterations in intestinal microbiota and short-chain fatty acids (SCFAs) were detected and analyzed. Finally, an integration analysis of colonic lipid metabolism with gene expression and intestinal microbiota was performed respectively. Result: Swimming pretreatment relieved bowel inflammation and minimized tumor formation. We demonstrated that prostaglandin E2 (PGE2)/PGE2 receptor 2 subtype (EP2) signaling as a potential regulatory target for swimming induces colonic lipid metabolites. Swimming-induced genera, Erysipelatoclostridium, Parabacteroides, Bacteroides, and Rikenellaceae_RC9_gut_group, induced intestinal SCFAs and affected the function of colonic lipid metabolites enriched in glycerophospholipid metabolism and choline metabolism in cancer. Conclusion: According to our experiments, swimming pretreatment can protect mice from CAC by intervention in the possible link between colonic lipid metabolites and PGE2/EP2 signaling. Further, swimming-induced genera and probiotics promoted glycerophospholipid metabolism and choline metabolism in cancer, the major constituents of colonic lipid metabolites, and increased SCFAs, which were also important mechanisms for the anti-inflammatory and anti-tumorigenic effects of swimming.

miR-203a-3p-DNMT3B feedback loop facilitates non-small cell lung cancer progression.

It has been reported that microRNA-203a-3p (miR-203a-3p) modulates cell proliferation, migration and invasion in a variety of cancer cell types. However, little is known about its role in lung cancer progression. The present study found that miR-203a-3p was downregulated in non-small cell lung cancer (NSCLC) cell lines and tissues. Overexpression of miR-203a-3p inhibits NSCLC cell proliferation, migration and invasion, and promotes cellular apoptosis in vitro. Restoration of miR-203a-3p expression in A549 and NCI-H520 cells enhances their chemosensitivity. Further experiments showed that DNA methyltransferase 3B (DNMT3B) was a direct target of miR-203a-3p. In addition, the present results revealed that promoter hypermethylation was the potential mechanism responsible for low miR-203a-3p expression in NSCLC. Notably, feedback regulation between miR-203a-3p and DNMT3B was observed in NSCLC. Moreover, Overexpression of miR-203a-3p reduces tumor growth in vivo. In summary, the present study has identified an miR-203a-3p-DNMT3B feedback loop that facilitates NSCLC progression.

Bacteria Associated With Phaeocystis globosa and Their Influence on Colony Formation.

Phaeocystis globosa (P. globosa) is one of the dominant algae during harmful algal blooms (HABs) in coastal regions of Southern China. P. globosa exhibits complex heteromorphic life cycles that could switch between solitary cells and colonies. The ecological success of P. globosa has been attributed to its colony formation, although underlying mechanisms remain unknown. Here, we investigated different bacterial communities associated with P. globosa colonies and their influence on colony formation of two P. globosa strains isolated from coastal waters of Guangxi (GX) and Shantou (ST). Eight operational taxonomic units (OTUs) were observed in ST co-cultures and were identified as biomarkers based on Linear discriminant analysis Effect Size (LEfSe) analysis, while seven biomarkers were identified in P. globosa GX co-cultures. Bacterial communities associated with the P. globosa GX were more diverse than those of the ST strain. The most dominant phylum in the two co-cultures was Proteobacteria, within which Marinobacter was the most abundant genus in both GX and ST co-cultures. Bacteroidota were only observed in the GX co-cultures and Planctomycetota were only observed in the ST co-cultures. Co-culture experiments revealed that P. globosa colony formation was not influenced by low and medium cell densities of Marinobacter sp. GS7, but was inhibited by high cell densities of Marinobacter sp. GS7. Overall, these results indicated that the associated bacteria are selected by different P. globosa strains, which may affect the colony formation and development of P. globosa.

Analysis of transcript-wide profile regulated by microsatellite instability of colorectal cancer.

Background: Microsatellite instability-high (MSI-H) is a form of genomic instability present in 15% of colorectal cancer (CRC) cases. Several differential gene analyses have been conducted on CRC; however, none have specifically explored the differentially expressed genes in MSI-H CRC. Research on the different gene expressions between MSI-H CRC and microsatellite stable (MSS) CRC, and their different patterns of metastasis will provide invaluable insights for diagnosis, prognosis, and treatment. Methods: In this study, the differential expression of 46,602 genes were analyzed across 613 different tissue samples from The Cancer Genome Atlas (TCGA)-colon adenocarcinoma (COAD) and TCGA-rectum adenocarcinoma (READ) as part of a gene association analysis. R package TCGAbiolinks (version 2.18.0) was used to download the data set, and DESeq2 (version 1.30.1) was used for the differential gene analysis. The resulting genes were then analyzed for shared pathways with R package clusterProfiler (version 3.0.4). Results: A total of 237 significantly differentially expressed genes (Padj<0.05) were found between MSI-H and MSS CRC. Differentially expressed genes include insulin like growth factor 2 (IGF2) and fibroblast growth factor 3 (FGF3), and the enriched pathways mostly involve hearing, digestive regulation, and neurogenesis.463 differentially expressed genes were found between metastatic and non-metastatic CRC. Notably differentially expressed genes in metastatic CRC include DEAD-box helicase 53 (DDX53) and adiponectin, C1Q and collagen domain containing (ADIPOQ), and enriched pathways include the immune system, cell adhesion, and cell signaling. For MSI-H CRC, a total of 34 genes were significantly differently expressed between metastatic and non-metastatic CRC. These include notum, palmitoleoyl-protein carboxylesterase (NOTUM), serpin family B member 2 (SERPINB2), and several keratin (KRT) genes, and the pathway analysis showed the major enrichment of the hormonal and secretion and regulation pathways. Of the differentially expressed genes in metastatic CRC, 25 were immunity related and include fatty acid binding protein 4 (FABP4), and the pathway analysis showed the enrichment of humoral immunity and lymphocyte regulation. Conclusions: Of the biologically plausible differentially expressed genes, the most notable were NOTUM, KRT6A, KRT14, SERPINB2, and serum amyloid A1 (SAA1). NOTUM, KRT6A, and KRT14 are active in the Wnt pathway. All five are also involved in various inflammation pathways.

Hepatic Fatty Acid Profiles Associated with Exposure to Emerging and Legacy Halogenated Contaminants in Two Harbor Seal Populations across the North Atlantic.

Fatty acids (FAs) have been extensively used as indicators of foraging ecology in marine mammals, yet their association with exposure to contaminants has rarely been investigated. The present study provided the first characterization of the relationship between hepatic FA profiles and exposure to a suite of contaminants in a sentinel species─the harbor seal (Phoca vitulina)─from the Gulf of Maine and the south coast of Sweden. FA profiles differed in the two seal populations, and the levels of legacy and alternative brominated flame retardants and polyhalogenated carbazoles were significantly elevated in Maine seals. Correlations between individual FAs and multiple flame retardants (FRs) and poly- and perfluoroalkyl substances (PFASs) were found in seals from both populations. Moreover, several FR and PFAS chemicals were significantly associated with the estimated desaturating enzyme activity inferred from the FA profiles. The ratios of poly to monounsaturated FAs (∑PUFAs/∑MUFAs) and those of unsaturated to saturated FAs (∑UFAs/∑SFAs) were significantly associated with HBBZ, PFHxS, or BDE 47 in seals from Maine and Sweden, whereas ∑n - 6/∑n - 3 PUFAs was significantly associated with BDE 154 and 36-CCZ in Swedish and Maine seals, respectively. Our results suggest the lipid metabolism-disrupting potential of these contaminants in marine mammals and warrant continuous biomonitoring and risk assessment, considering the critical role of PUFAs in vital biological processes.

Glycinebetaine: a versatile protectant to improve rice performance against aluminium stress by regulating aluminium uptake and translocation.

KEY MESSAGE: Glycinebetaine alleviates the detrimental effects of aluminium stress by regulating aluminium uptake and translocation, maintaining PSII activity, and activating the oxidative defence, thereby maintaining the growth and development of rice. Aluminium (Al) toxicity is one of the primary growth-limiting factors that limits plant growth and crop productivity in acidic soils. Rice (Oryza sativa L.) plants are susceptible to Al stress and do not naturally accumulate glycinebetaine (GB), one of the most effective protectants. Therefore, the objective of this study was to investigate whether exogenous GB can ameliorate the detrimental effects of Al stress on rice plants. Our results showed that the growth, development and biomass of rice were clearly inhibited under Al stress. However, exogenous GB application increased rice shoot growth and photosynthetic pigments contents, maintained photosystem II (PSII) activity, and activated the antioxidant defence system under Al stress. More importantly, GB may mediate the expression of Al uptake- and translocation-related genes, including OsALS1, OsNrat1, OsSTAR1 and OsSTAR2, and the galacturonic acid contents in rice roots under Al stress. Therefore, our findings highlight exogenous GB application is a valid approach to effectively combat Al toxicity by regulating physiological and biochemical processes in crops.

Ajuba transactivates N-cadherin expression in colorectal cancer cells through interaction with Twist.

Ajuba is a multiple LIM domain-containing protein and functions as a transcriptional coregulator to modulate many gene expressions in various cellular processes. Here, we describe that the LIM domain of Ajuba interacts with Twist, and the Twist box is a pivotal motif for the interaction. Biologically, Ajuba enhances transcription of target gene N-cadherin as an obligate coactivator of Twist. The enhancement is achieved by binding to the E-box element within N-cadherin promoter as revealed by luciferase reporter and chromatin immunoprecipitation assays. Mechanistic investigation demonstrates that Ajuba recruits CBP and Twist to form a ternary complex at the Twist target promoter region and concomitantly enhances histone acetylation at these sites. These findings identify that Twist is a new interacting protein of Ajuba and Ajuba/Twist/CBP ternary complex may be a potential treatment strategy for Twist-related tumour metastasis.

Online Clinical Consultation as a Utility Tool for Managing Medical Crisis During a Pandemic: Retrospective Analysis on the Characteristics of Online Clinical Consultations During the COVID-19 Pandemic.

Coronavirus disease 2019 (COVID-19) is a newly-identified infectious diseases that has rapidly spread throughout the world with rising fatalities with declaration by World Health Organization as the pandemic. Online consultations have been shown to alleviate the pandemic with our study aims to demonstrate whether online consultation can be a solution for acute health crisis. Retrospective analysis of the characteristics of online consultations through two primary care online-consultation platforms during COVID-19 pandemic was performed at the Third Affiliated Hospital of Sun Yat-Sen University, which led the assessment of COVID-19-symptoms patients in Guangzhou. The 3473 online consultations were divided into pre-pandemic and pandemic period groups with Chi-square test as statistical analysis method. The number of online consultations has increased with diagnosis of upper respiratory tract infection, psychological conditions, COVID-19-related investigations and interventions. The increased online consultations met the increased demand of the relevant clinical services and reduced the overwhelming hospital presentations, thus decreasing the potential COVID-19 spread inside the major tertiary hospital and sparing the resources for acute crisis management. The epidemiology and disease characteristics of online consultations during the pandemic have been demonstrated with identification of the enabling factors and potential barriers in improving online healthcare in China with online consultation model being a durable solution for pandemic in future.

Contra-Directional Expression of Plasma Superoxide Dismutase with Lipoprotein Cholesterol and High-Sensitivity C-reactive Protein as Important Markers of Parkinson's Disease Severity.

Aim: Oxidative stress and inflammation play critical roles in the neuropathogenesis of PD. We aimed to evaluate oxidative stress and inflammation status by measuring serum superoxide dismutase (SOD) with lipoprotein cholesterol and high-sensitivity C-reactive protein (hsCRP) respectively in PD patients, and explore their correlation with the disease severity. Methods: We performed a cross-sectional study that included 204 PD patients and 204 age-matched healthy controls (HCs). Plasma levels of SOD, hsCRP, total cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured. A series of neuropsychological assessments were performed to rate the severity of PD. Results: The plasma levels of SOD (135.7 ± 20.14 vs. 147.2 ± 24.34, P < 0.0001), total cholesterol, HDL-C and LDL-C in PD were significantly lower than those in HCs; the hsCRP level was remarkably increased in PD compared to HC (2.766 ± 3.242 vs. 1.637 ± 1.597, P < 0.0001). The plasma SOD was negatively correlated with the hsCRP, while positively correlated with total cholesterol, HDL-C, and LDL-C in PD patients. The plasma SOD were negatively correlated with H&Y, total UPDRS, UPDRS (I), UPDRS (II), and UPDRS (III) scores, but positively correlated with MoCA and MMSE scores. Besides, hsCRP was negatively correlated with MoCA; while total cholesterol, HDL-C and LDL-C were positively correlated with the MoCA, respectively. Conclusion: Our findings suggest that lower SOD along with cholesterol, HDL-C and LDL-C, and higher hsCRP levels might be important markers to assess the PD severity. A better understanding of SOD and hsCRP may yield insights into the pathogenesis of PD.

Advances in the Research of Risk Factors and Prodromal Biomarkers of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. With the advent of an aging population and improving life expectancy worldwide, the number of PD patients is expected to increase, which may lead to an urgent need for effective preventive and diagnostic strategies for PD. Although there is increasing research regarding the pathogenesis of PD, there is limited knowledge regarding the prevention of PD. Moreover, the diagnosis of PD depends on clinical criteria, which require the occurrence of bradykinesia and at least one symptom of rest tremor or rigidity. However, converging evidence from clinical, genetic, neuropathological, and imaging studies suggests the initiation of PD-specific pathology prior to the initial presentation of these classical motor clinical features by years or decades. This latent stage of neurodegeneration in PD is a particularly important stage for effective neuroprotective therapies, which might retard the progression or prevent the onset of PD. Therefore, the exploration of risk factors and premotor biomarkers is not only crucial to the early diagnosis of PD but is also helpful in the development of effective neuroprotection and health care strategies for appropriate populations at risk for PD. In this review, we searched and summarized ∼249 researches and 31 reviews focusing on the risk factors and prodromal biomarkers of PD and published in MEDLINE.

Targeted Mutation (R100W) of the Gene Encoding NGF Leads to Deficits in the Peripheral Sensory Nervous System.

Nerve growth factor (NGF) exerts multifaceted functions through different stages of life. A missense mutation (R100W) in the beta-NGF gene was found in hereditary sensory autonomic neuropathy V (HSAN V) patients with severe loss of pain perception but without overt cognitive impairment. To better understand the pathogenesis of HSAN V, we generated the first NGFR100W knock in mouse model for HSAN V. We found that the homozygotes exhibited a postnatal lethal phenotype. A majority of homozygous pups died within the first week. Some homozygous pups could ingest more milk and survived up to 2 months by reducing litter size. Whole mount in situ hybridization using E10.5 embryos revealed that, compared to wild type, R100W mutation did not alter the gene expression patterns of TrkA and P75NTR in the homozygotes. We also found that the homozygotes displayed normal embryonic development of major organs (heart, lung, liver, kidney, and spleen). Furthermore, the homozygotes exhibited severe loss of PGP9.5-positive intra-epidermal sensory fibers. Taken together, our results suggest that, as with HSAN V patients, the R100W mutation primarily affects the peripheral sensory nervous system in the mouse model. This novel mouse model makes it possible to further study in vivo how NGFR100W uncouple trophic function from nociception of NGF.

Avermectin biosynthesis: stable functional expression of branched chain α-keto acid dehydrogenase complex from Streptomyces avermitilis in Escherichia coli by selectively regulating individual subunit gene expression.

OBJECTIVE: To improve the production of short branched-chain acyl-CoAs for avermectin biosynthesis, the functional expression of the branched chain α-keto acid dehydrogenase complex (BKDH) from Streptomyces avermitilis was systematically optimized by selectively regulating individual subunit expression in Escherichia coli. RESULTS: Functional expression of the BKDH complex was achieved by independent and selective optimization of individual subunit genes of the complex. Codon optimization significantly improved the expression of complex component proteins BkdH and LpdA1 but expression of BkdF and BkdG depended on coexpression of the bkdH gene. The optimized BKDH complex supplied sufficient short branched-chain acyl-CoA to synthesize phlorisovalerophenone, a key intermediate in bitter acid (humulone) synthesis. We also developed a novel p15A origin-derived high-copy-number vector system for expression; the yield of PIVP was 350 ng/mOD. CONCLUSION: Through optimization strategies, we obtained stable, functional expression of the BKDH complex in E. coli, which could be applied in the heterologous production of numerous high-value-added chemicals, especially polyketides.