TREM2 alleviates white matter injury after traumatic brain injury in mice might be mediated by regulation of DHCR24/LXR pathway in microglia.

BACKGROUND: White matter injury (WMI) is an important pathological process after traumatic brain injury (TBI). The correlation between white matter functions and the myeloid cells expressing triggering receptor-2 (TREM2) has been convincingly demonstrated. Moreover, a recent study revealed that microglial sterol metabolism is crucial for early remyelination after demyelinating diseases. However, the potential roles of TREM2 expression and microglial sterol metabolism in WMI after TBI have not yet been explored. METHODS: Controlled cortical injury was induced in both wild-type (WT) and TREM2 depletion (TREM2 KO) mice to simulate clinical TBI. COG1410 was used to upregulate TREM2, while PLX5622 and GSK2033 were used to deplete microglia and inhibit the liver X receptor (LXR), respectively. Immunofluorescence, Luxol fast blue staining, magnetic resonance imaging, transmission electron microscopy, and oil red O staining were employed to assess WMI after TBI. Neurological behaviour tests and electrophysiological recordings were utilized to evaluate cognitive functions following TBI. Microglial cell sorting and transcriptomic sequencing were utilized to identify alterations in microglial sterol metabolism-related genes, while western blot was conducted to validate the findings. RESULTS: TREM2 expressed highest at 3 days post-TBI and was predominantly localized to microglial cells within the white matter. Depletion of TREM2 worsened aberrant neurological behaviours, and this phenomenon was mediated by the exacerbation of WMI, reduced renewal of oligodendrocytes, and impaired phagocytosis ability of microglia after TBI. Subsequently, the upregulation of TREM2 alleviated WMI, promoted oligodendrocyte regeneration, and ultimately facilitated the recovery of neurological behaviours after TBI. Finally, the expression of DHCR24 increased in TREM2 KO mice after TBI. Interestingly, TREM2 inhibited DHCR24 and upregulated members of the LXR pathway. Moreover, LXR inhibition could partially reverse the effects of TREM2 upregulation on electrophysiological activities. CONCLUSIONS: We demonstrate that TREM2 has the potential to alleviate WMI following TBI, possibly through the DHCR24/LXR pathway in microglia.

Qilong capsule prevents myocardial ischemia/reperfusion injury by inhibiting platelet activation via the platelet CD36 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Qilong capsule (QC) is developed from the traditional Chinese medicine formula Buyang Huanwu Decoction, which has been clinically used to invigorate Qi and promote blood circulation to eliminate blood stasis. Myocardial ischemia‒reperfusion injury (MIRI) can be attributed to Qi deficiency and blood stasis. However, the effects of QC on MIRI remain unclear. AIM OF THE STUDY: This study aimed to investigate the protective effect and possible mechanism of QC on platelet function in MIRI rats. MATERIALS AND METHODS: The left anterior descending artery of adult Sprague‒Dawley rats was ligated for 30 min and then reperfused for 120 min with or without QC treatment. Then, the whole blood viscosity, plasma viscosity, coagulation, platelet adhesion rate, platelet aggregation, and platelet release factors were evaluated. Platelet CD36 and its downstream signaling pathway-related proteins were detected by western blotting. Furthermore, the active components of QC and the molecular mechanism by which QC regulates platelet function were assessed via molecular docking, platelet aggregation tests in vitro and BLI analysis. RESULTS: We found that QC significantly reduced the whole blood viscosity, plasma viscosity, platelet adhesion rate, and platelet aggregation induced by ADP or AA in rats with MIRI. The inhibition of platelet activation by QC was associated with reduced levels of ß-TG, PF-4, P-selectin and PAF. Mechanistically, QC effectively attenuated the expression of platelet CD36 and thus inhibited the activation of Src, ERK5, and p38. The active components of QC apparently suppressed platelet aggregation in vitro and regulated the CD36 signaling pathway. CONCLUSIONS: QC improves MIRI-induced hemorheological disorders, which might be partly attributed to the inhibition of platelet activation via CD36-mediated platelet signaling pathways.

Risk of infection with arboviruses in a healthy population in Pakistan based on seroprevalence.

Infectious diseases caused by arboviruses are a public health concern in Pakistan. However, the studies on data prevalence and threats posed by arboviruses are limited. This study investigated the seroprevalence of arboviruses in a healthy population in Pakistan, including severe fever with thrombocytopenia syndrome virus (SFTSV), Crimean-Congo haemorrhagic fever virus (CCHFV), Tamdy virus (TAMV), and Karshi virus (KSIV) based on a newly established luciferase immunoprecipitation system (LIPS) assays, and Zika virus (ZIKV) by enzyme-linked immunosorbent assays (ELISA). Neutralizing activities against these arboviruses were further examined from the antibody positive samples. The results showed that the seroprevalence of SFTSV, CCHFV, TAMV, KSIV, and ZIKV was 17.37%, 7.58%, 4.41%, 1.10%, and 6.48%, respectively, and neutralizing to SFTSV (1.79%), CCHFV (2.62%), and ZIKV (0.69%) were identified, as well as to the SFTSV-related Guertu virus (GTV, 0.83%). Risk factors associated with the incidence of exposure and levels of antibody response were analysed. Moreover, co-exposure to different arboviruses was demonstrated, as thirty-seven individuals were having antibodies to multiple viruses and thirteen showed neutralizing activity. Males, individuals aged ≤ 40 years, and outdoor workers had high risk of exposure to arboviruses. All these results reveal the substantial risks of infection with arboviruses in Pakistan, and indicate the threat from co-exposure to multiple arboviruses. The findings raise the need for further epidemiologic investigation in expanded regions and populations and the necessity to improve health surveillance in Pakistan.

Engineering and application of LacI mutants with stringent expressions.

Optimal transcriptional regulatory circuits are expected to exhibit stringent control, maintaining silence in the absence of inducers while exhibiting a broad induction dynamic range upon the addition of effectors. In the Plac /LacI pair, the promoter of the lac operon in Escherichia coli is characterized by its leakiness, attributed to the moderate affinity of LacI for its operator target. In response to this limitation, the LacI regulatory protein underwent engineering to enhance its regulatory properties. The M7 mutant, carrying I79T and N246S mutations, resulted in the lac promoter displaying approximately 95% less leaky expression and a broader induction dynamic range compared to the wild-type LacI. An in-depth analysis of each mutation revealed distinct regulatory profiles. In contrast to the wild-type LacI, the M7 mutant exhibited a tighter binding to the operator sequence, as evidenced by surface plasmon resonance studies. Leveraging the capabilities of the M7 mutant, a high-value sugar biosensor was constructed. This biosensor facilitated the selection of mutant galactosidases with approximately a seven-fold improvement in specific activity for transgalactosylation. Consequently, this advancement enabled enhanced biosynthesis of galacto-oligosaccharides (GOS).

In Vivo Pharmacokinetic Study of Polygonatum cyrtonema Polysaccharide DPC1 after Oral and Intraperitoneal Administration.

(1) Background: Polygonatum cyrtonema is a medicinal plant, and its polysaccharides are used for immunomodulation and the treatment of hyperglycemia. Investigation of the tissue distribution and pharmacokinetics of P. cyrtonema polysaccharide can further elucidate its pharmacological mechanisms. (2) Methods: A fluorescence-labeling approach using rhodamine B (RhB) as a fluorescent molecular probe was used for the quantitative assessment of the polysaccharide from dried P. cyrtonema (DPC1) samples, and the pharmacokinetics and tissue distribution of DPC1 were evaluated in mice after intraperitoneal or oral administration. (3) Results: DPC1 was successfully labeled with RhB, showing degrees of fluorescence labeling at 0.453% and 0.568% as determined by the ultraviolet and enzyme marker methods, respectively. DPC1-RhB was rapidly absorbed into the bloodstream after oral and intraperitoneal administration. Pharmacokinetic characteristics showed that oral administration and intraperitoneal administration were consistent with the features of a two-compartment model. (4) Conclusion: After administration, DPC1-RhB was primarily distributed in the tissues of the heart, spleen, and lung, indicating that the drug has a targeted effect on these tissues. Overall, the findings provide a comprehensive reference for the in vivo distribution of DPC1, together with a foundation for further elucidation of its pharmacological mechanisms and the development and application of DPC1 formulations.

Artificial Biosynthetic Pathway for Efficient Synthesis of Vanillin, a Feruloyl-CoA-Derived Natural Product from Eugenol.

Eugenol, the main component of essential oil from the Syzygium aromaticum clove tree, has great potential as an alternative bioresource feedstock for biosynthesis purposes. Although eugenol degradation to ferulic acid was investigated, an efficient method for directly converting eugenol to targeted natural products has not been established. Herein we identified the inherent inhibitions by simply combining the previously reported ferulic acid biosynthetic pathway and vanillin biosynthetic pathway. To overcome this, we developed a novel biosynthetic pathway for converting eugenol into vanillin, by introducing cinnamoyl-CoA reductase (CCR), which catalyzes conversion of coniferyl aldehyde to feruloyl-CoA. This approach bypasses the need for two catalysts, namely coniferyl aldehyde dehydrogenase and feruloyl-CoA synthetase, thereby eliminating inhibition while simplifying the pathway. To further improve efficiency, we enhanced CCR catalytic efficiency via directed evolution and leveraged an artificialvanillin biosensor for high-throughput screening. Switching the cofactor preference of CCR from NADP+ to NAD+ significantly improved pathway efficiency. This newly designed pathway provides an alternative strategy for efficiently biosynthesizing feruloyl-CoA-derived natural products using eugenol.

Hypoxic Exosomal circPLEKHM1-Mediated Crosstalk between Tumor Cells and Macrophages Drives Lung Cancer Metastasis.

Intercellular communication often relies on exosomes as messengers and is critical for cancer metastasis in hypoxic tumor microenvironment. Some circular RNAs (circRNAs) are enriched in cancer cell-derived exosomes, but little is known about their ability to regulate intercellular communication and cancer metastasis. Here, by systematically analyzing exosomes secreted by non-small cell lung cancer (NSCLC) cells, a hypoxia-induced exosomal circPLEKHM1 is identified that drives NSCLC metastasis through polarizing macrophages toward to M2 type. Mechanistically, exosomal circPLEKHM1 promoted PABPC1-eIF4G interaction to facilitate the translation of the oncostatin M receptor (OSMR), thereby promoting macrophage polarization for cancer metastasis. Importantly, circPLEKHM1-targeted therapy significantly reduces NSCLC metastasis in vivo. circPLEKHM1 serves as a prognostic biomarker for metastasis and poor survival in NSCLC patients. This study unveils a new circRNA-mediated mechanism underlying how cancer cells crosstalk with macrophages within the hypoxic tumor microenvironment to promote metastasis, highlighting the importance of exosomal circPLEKHM1 as a prognostic biomarker and therapeutic target for lung cancer metastasis.

Dual antiplatelet therapy after intravenous thrombolysis for patients with minor ischemic stroke：A meta-analysis.

OBJECTIVE: Intravenous thrombolysis (IVT) has been shown to effectively decrease both the disability rate and mortality associated with acute ischemic stroke, however, there is also a risk of vascular re-occlusion. Antiplatelet therapy can mitigate this risk. Nevertheless, there are no relevant guidelines recommending whether the administration of dual antiplatelet therapy (DAPT) with aspirin and clopidogrel can be performed following thrombolysis. The aim of this study was to conduct a meta-analysis utilizing multiple studies in order to assess the effectiveness and safety of DAPT after IVT in cases of acute mild ischemic stroke (AMIS). METHODS: A comprehensive search on English literature published was performed on databases including PubMed, Embase, Web of Science, and Cochrane up until September 1, 2023. All cases were ischemic stroke patients who underwent IVT within a 4.5-hour timeframe and had a National Institutes of Health Stroke Scale (NIHSS) score of ≤5 (or 3) upon admission. The primary efficacy endpoint is the 90-day Modified Rankin Scale (mRS) Score (MRS score 0-1), while the primary safety endpoint encompassed the occurrence of symptomatic intracranial hemorrhage (SICH) and 90-day mortality. The study's secondary objective is the recurrence of any type of stroke (hemorrhagic and ischemic) within a 90-day period. The included studies underwent an evaluation of bias risk using the Newcastle Ottawa scale. Risk ratios (RRs) and CIs were calculated using a random effects model, and the findings and heterogeneity among the included studies were visually presented on a forest plot. (There was a protocol registration (PROSPERO):). RESULTS: Out of the 1081 studies that were obtained, only 3 met the criteria and were included in the meta-analysis (657 patients in total). The findings indicate that, there was a significant difference in the mRS of 0-1 between single antiplatelet therapy (SAPT) with only aspirin or clopidogrel and DAPT with aspirin and clopidogrel ((RR,1.11[95%CI,0.99-1.24];P=0.07;I2=55%), and no significant difference in stroke recurrence after 90 days or 1 year ((RR,0.94[95%CI,0.41-2.16];P=0.89;I2=30%); Regarding safety evaluation, the results showed no significant difference in the SICH (RR,0.65[95%CI,0.11-3.97];P=0.64;I2=0%) and the incidence of mortality (RR,0.97[95%CI,0.19-4.96];P=0.97;I2=0%) between the two groups. CONCLUSIONS: For patients with acute mild ischemic stroke (AMIS), in conjunction with DAPT after IVT can improve the 90-day prognosis, without increasing the risk of intracranial hemorrhage and 90-day mortality. However, it cannot reduce the risk of stroke recurrence.

Viromes of Haemaphysalis longicornis reveal different viral abundance and diversity in free and engorged ticks.

Haemaphysalis longicornis ticks, commonly found in East Asia, can transmit various pathogenic viruses, including the severe fever with thrombocytopenia syndrome virus (SFTSV) that has caused febrile diseases among humans in Hubei Province. However, understanding of the viromes of H. longicornis was limited, and the prevalence of viruses among H. longicornis ticks in Hubei was not well clarified. This study investigates the viromes of both engorged (fed) and free (unfed) H. longicornis ticks across three mountainous regions in Hubei Province from 2019 to 2020. RNA-sequencing analysis identified viral sequences that were related to 39 reference viruses belonging to unclassified viruses and seven RNA viral families, namely Chuviridae, Nairoviridae, Orthomyxoviridae, Parvoviridae, Phenuiviridae, Rhabdoviridae, and Totiviridae. Viral abundance and diversity in these ticks were analysed, and phylogenetic characteristics of the Henan tick virus (HNTV), Dabieshan tick virus (DBSTV), Okutama tick virus (OKTV), and Jingmen tick virus (JMTV) were elucidated based on their full genomic sequences. Prevalence analysis demonstrated that DBSTV was the most common virus found in individual H. longicornis ticks (12.59%), followed by HNTV (0.35%), whereas JMTV and OKTV were not detected. These results improve our understanding of H. longicornis tick viromes in central China and highlight the role of tick feeding status and geography in shaping the viral community. The findings of new viral strains and their potential impact on public health raise the need to strengthen surveillance efforts for comprehensively assessing their spillover potentials.

Predictive value of hyponatremia for short-term mortality in supratentorial spontaneous intracerebral hemorrhage: a single center study.

Background: Hyponatremia is a common electrolyte disturbance in patients with neurological disease; however, its predictive role for outcome in patients with supratentorial spontaneous intracerebral hemorrhage (sICH) is controversial. This study aims to explore the association between hyponatremia within 7 days after bleeding and 90-day mortality in patients with supratentorial sICH. Methods: A retrospective analysis was conducted at our institution. Patients with sICH meeting the inclusion criteria were enrolled in this study. Multivariate regression analyses were performed to determine the predictive value of hyponatremia (serum sodium <135 mmol/L) for 90-day mortality and functional outcome. Subgroup analysis was performed based on the degree and duration of hyponatremia and therapeutic strategies. The Spearman correlation test was performed to explore the relationship between hyponatremia severity and duration with variables in a multivariate regression model. Kaplan-Meier curve was depicted to reveal the relationship between hyponatremia and mortality. The receiver operating characteristic (ROC) curve was plotted to show the diagnostic effect of the minimum concentration of serum sodium (sodiummin) on 90-day mortality. Results: A total of 960 patients were enrolled, 19.6% (188) of whom were patients with hyponatremia and 26.0% (250) had 90-day mortality. The incidence of hyponatremia was roughly 2.5 times in non-survivors compared with survivors (34.8% vs. 14.2%). Multivariate regression analysis revealed that hyponatremia was the independent predictor of 90-day mortality (OR 2.763, 95%CI 1.836-4.157) and adverse outcome (OR 3.579, 95%CI 2.332-6.780). Subgroup analysis indicated an increased trend in mortality risk with both duration (more or less than 48 h) and severity of hyponatremia (mild, moderate, and severe) and confirmed the predictive value of hyponatremia for mortality in patients undergoing surgical intervention (external ventricular drainage, craniotomy, and decompressive craniectomy; all p < 0.05). The Spearman correlation test indicated no moderate or strong relationship between hyponatremia severity and duration with other variables in the multivariate model (all |rs| < 0.4). The ROC curve suggested the moderate diagnostic performance of sodiummin for mortality in both general patients and subgroups of therapeutic method patients (AUC from 0.6475 to 0.7384). Conclusion: Hyponatremia occurring in the first 7 days after bleeding is an independent predictor of 90-day morality and adverse outcome. Rigorous electrolyte scrutiny in patients treated surgically is required.

Connectome-based predictive modeling of Internet addiction symptomatology.

Internet addiction symptomatology (IAS) is characterized by persistent and involuntary patterns of compulsive Internet use, leading to significant impairments in both physical and mental well-being. Here, a connectome-based predictive modeling approach was applied to decode IAS from whole-brain resting-state functional connectivity in healthy population. The findings showed that IAS could be predicted by the functional connectivity between prefrontal cortex with the cerebellum and limbic lobe and connections of the occipital lobe with the limbic lobe and insula lobe. The identified edges associated with IAS exhibit generalizability in predicting IAS within an independent sample. Furthermore, we found that the unique contributing network, which predicted IAS in contrast to the prediction networks of alcohol use disorder symptomatology (the range of symptoms and behaviors associated with alcohol use disorder), prominently comprised connections involving the occipital lobe and other lobes. The current data-driven approach provides the first evidence of the predictive brain features of IAS based on the organization of intrinsic brain networks, thus advancing our understanding of the neurobiological basis of Internet addiction disorder (IAD) susceptibility, and may have implications for the timely intervention of people potentially at risk of IAD.

68Ga-FAPI PET imaging monitors response to combined TGF-ßR inhibition and immunotherapy in metastatic colorectal cancer.

BACKGROUNDImproving and predicting tumor response to immunotherapy remains challenging. Combination therapy with a transforming growth factor-ß receptor (TGF-ßR) inhibitor that targets cancer-associated fibroblasts (CAFs) is promising for the enhancement of efficacy of immunotherapies. However, the effect of this approach in clinical trials is limited, requiring in vivo methods to better assess tumor responses to combination therapy.METHODSWe measured CAFs in vivo using the 68Ga-labeled fibroblast activation protein inhibitor-04 (68Ga-FAPI-04) for PET/CT imaging to guide the combination of TGF-ß inhibition and immunotherapy. One hundred thirty-one patients with metastatic colorectal cancer (CRC) underwent 68Ga-FAPI and 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging. The relationship between uptake of 68Ga-FAPI and tumor immunity was analyzed in patients. Mouse cohorts of metastatic CRC were treated with the TGF-ßR inhibitor combined with KN046, which blocks programmed death ligand 1 (PD-L1) and CTLA-4, followed by 68Ga-FAPI and 18F-FDG micro-PET/CT imaging to assess tumor responses.RESULTSPatients with metastatic CRC demonstrated high uptake rates of 68Ga-FAPI, along with suppressive tumor immunity and poor prognosis. The TGF-ßR inhibitor enhanced tumor-infiltrating T cells and significantly sensitized metastatic CRC to KN046. 68Ga-FAPI PET/CT imaging accurately monitored the dynamic changes of CAFs and tumor response to combined the TGF-ßR inhibitor with immunotherapy.CONCLUSION68Ga-FAPI PET/CT imaging is powerful in assessing tumor immunity and the response to immunotherapy in metastatic CRC. This study supports future clinical application of 68Ga-FAPI PET/CT to guide precise TGF-ß inhibition plus immunotherapy in CRC patients, recommending 68Ga-FAPI and 18F-FDG dual PET/CT for CRC management.TRIAL REGISTRATIONCFFSTS Trial, ChiCTR2100053984, Chinese Clinical Trial Registry.FUNDINGNational Natural Science Foundation of China (82072695, 32270767, 82272035, 81972260).

Epidemiological surveys revealed the risk of TAMV spill-over from ticks to hosts.

BACKGROUND: Tick-borne viral diseases have become an increasingly important public health concern. Tamdy virus (TAMV) is a tick-borne virus of the genus Orthonairovirus in the family Nairoviridae. While some studies have suggested that TAMV is a pathogen associated with human febrile illness, its epidemiology and the risk of TAMV spill-over remain poorly understood. METHODS: Ticks were collected in Xinjiang, China, and grouped into pools. RT-PCR assays were used to detect TAMV RNA in these pools. The seroprevalence of TAMV was investigated using Immunofluorescence assays, Western blotting, and Luciferase immunoprecipitation system (LIPS) assays. RESULTS: TAMV RNA was detected in 17 out of 363 tick pools, resulting in a minimum infection rate (MIR) of 4.7%. Hyalomma asiaticum and Dermacentor nuttalli were identified as major tick vectors of TAMV. Phylogenetic analysis demonstrated that TAMV strains from Xinjiang are closely related to strains from other countries. Seroprevalence studies showed that TAMV exposure has been occurring in Xinjiang since at least 2006. Antibody responses to TAMV were detected in 1.1% (26/2296) of animals, including domestic animals and wild rodents. The seropositivity rates were as follows: sheep (1.7%), dog (2.3%), Marmota monax (0.8%), Meriones meridianus (3.5%). CONCLUSIONS: The research findings reveal that TAMV can be transmitted by ticks to various animal species, posing a significant public health risk. The wide distribution of TAMV and its tick vectors emphasise the importance of early preparedness and control measures. This study highlights the necessity for maintaining vigilance in addressing emerging zoonotic diseases transmitted by ticks.

Development of recombinant rotavirus carrying herpes simplex virus 2 glycoprotein D gene based on reverse genetics technology.

Vaccine development for herpes simplex virus 2 (HSV-2) has been attempted, but no vaccines are yet available. A plasmid-based reverse genetics system for Rotavirus (RV), which can cause gastroenteritis, allows the generation of recombinant RV containing foreign genes. In this study, we sought to develop simian RV (SA11) as a vector to express HSV-2 glycoprotein D (gD2) and evaluated its immunogenicity in mice. We generated the recombinant SA11-gD2 virus (rSA11-gD2) and confirmed its ability to express gD2 in vitro. The virus was orally inoculated into suckling BALB/c mice and into 8-week-old mice. Serum IgG and IgA titers against RV and gD2 were measured by ELISA. In the 8-week-old mice inoculated with rSA11-gD2, significant increases in not only antibodies against RV but also IgG against gD2 were demonstrated. In the suckling mice, antibodies against RV were induced, but gD2 antibody was not detected. Diarrhea observed after the first inoculation of rSA11-gD2 in suckling mice was similar to that induced by the parent virus. A gD2 expressing simian RV recombinant, which was orally inoculated, induced IgG against gD2. This strategy holds possibility for genital herpes vaccine development.

Nanobodies in cytokine­mediated immunotherapy and immunoimaging (Review).

Cytokines are the main regulators of innate and adaptive immunity, mediating communications between the cells of the immune system and regulating biological functions, including cell motility, differentiation, growth and apoptosis. Cytokines and cytokine receptors have been used in the treatment of tumors and autoimmune diseases, and to intervene in cytokine storms. Indeed, the use of monoclonal antibodies to block cytokine­receptor interactions, as well as antibody­cytokine fusion proteins has exhibited immense potential for the treatment of tumors and autoimmune diseases. Compared with these traditional types of antibodies, nanobodies not only maintain a high affinity and specificity, but also have the advantages of high thermal stability, a high capacity for chemical manipulation, low immunogenicity, good tissue permeability, rapid clearance and economic production. Thus, nanobodies have extensive potential for use in the diagnosis and treatment of cytokine­related diseases. The present review summarizes the application of nanobodies in cytokine­mediated immunotherapy and immunoimaging.

The application of weighted gene co-expression network analysis and support vector machine learning in the screening of Parkinson's disease biomarkers and construction of diagnostic models.

Background: This study aims to utilize Weighted Gene Co-expression Network Analysis (WGCNA) and Support Vector Machine (SVM) algorithm for screening biomarkers and constructing a diagnostic model for Parkinson's disease. Methods: Firstly, we conducted WGCNA analysis on gene expression data from Parkinson's disease patients and control group using three GEO datasets (GSE8397, GSE20163, and GSE20164) to identify gene modules associated with Parkinson's disease. Then, key genes with significantly differential expression from these gene modules were selected as candidate biomarkers and validated using the GSE7621 dataset. Further functional analysis revealed the important roles of these genes in processes such as immune regulation, inflammatory response, and cell apoptosis. Based on these findings, we constructed a diagnostic model by using the expression data of FLT1, ATP6V0E1, ATP6V0E2, and H2BC12 as inputs and training and validating the model using SVM algorithm. Results: The prediction model demonstrated an AUC greater than 0.8 in the training, test, and validation sets, thereby validating its performance through SMOTE analysis. These findings provide strong support for early diagnosis of Parkinson's disease and offer new opportunities for personalized treatment and disease management. Conclusion: In conclusion, the combination of WGCNA and SVM holds potential in biomarker screening and diagnostic model construction for Parkinson's disease.

Composition of Polygonatum zanlanscianense Pamp. Steam and Leaf Phenolic Extract and Its Protective Mechanism on t-BHP-Induced Oxidative Damage of HepG2 Cells.

Plant phenolic compounds have attracted considerable attention because of their health benefits. This study aimed to investigate the composition and antioxidant activity of phenol extracts from Polygonatum zanlanscianense Pamp. steam and leaf (PPP). The FTIR, UPLC-Q-Obtrip-MS, and HPLC-DAD methods were used to analyze the composition of PPP, and 20 phenolic compounds were preliminarily identified. Among them, the contents of hyperin, astragalin, and diosmetin levels were the highest. Treatment with PPP can significantly reduce t-BHP-induced cell damage in HepG2 cells, reactive oxygen species (ROS) accumulation, and malondialdehyde (MDA) content. Meanwhile, the superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px) activities can be increased. Moreover, PPP enhanced Nrf2 expression, which was consistent with that of heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and NAD(P)H quinone oxidoreductase-1 (NQO1), whereas the expression of Keap1, the Nrf2 inhibitor, was decreased. All findings indicate that PPP can serve as a natural bioactive substance for preventing oxidative stress.

Photoreduction of Aqueous Protons Coupling with Alcohol Oxidation on a S-Scheme Heterojunction Photocatalyst MnO/Carbon Nitride.

Crystalline carbon nitride (CCN), derived from amorphous polymeric CN, is considered as a new generation of metal-free photocatalyst because of its high crystallinity. In order to further promote the photocatalytic performance of CCN, p-type MnO nanoparticles are in situ synthesized and merged with n-type CCN through a one-pot process to form p-n heterojunction. The formed interfacial electric field between the semiconductors with different work functions efficiently breaks the coulomb interaction between MnO and CCN. The prepared catalysts exhibit drastically increased photocatalytic hydrogen evolution (PHE) activity integrated with oxidation of alkyl and aryl alcohols under irradiation of visible light. In the aqueous solution of benzyl alcohol (BzOH), the hydrogen generation rate over MnO/CCN (39.58 µmol h-1 ) is nearly 7 times and 37 times that of pure CCN (5.76 µmol h-1 ) and CN (1.06 µmol h-1 ), respectively, combining with oxidation of BzOH to benzaldehyde. This work proposes an avenue for in situ construction of a novel 2D material-based S-scheme heterojunction and extends its application in solar energy conservation and utilization.