USP16 is an ISG15 cross-reactive deubiquitinase that targets pro-ISG15 and ISGylated proteins involved in metabolism.

Interferon-induced ubiquitin (Ub)-like modifier ISG15 covalently modifies host and viral proteins to restrict viral infections. Its function is counteracted by the canonical deISGylase USP18 or Ub-specific protease 18. Notwithstanding indications for the existence of other ISG15 cross-reactive proteases, these remain to be identified. Here, we identify deubiquitinase USP16 as an ISG15 cross-reactive protease by means of ISG15 activity-based profiling. Recombinant USP16 cleaved pro-ISG15 and ISG15 isopeptide-linked model substrates in vitro, as well as ISGylated substrates from cell lysates. Moreover, interferon-induced stimulation of ISGylation was increased by depletion of USP16. The USP16-dependent ISG15 interactome indicated that the deISGylating function of USP16 may regulate metabolic pathways. Targeted enzymes include malate dehydrogenase, cytoplasmic superoxide dismutase 1, fructose-bisphosphate aldolase A, and cytoplasmic glutamic-oxaloacetic transaminase 1. USP16 may thus contribute to the regulation of a subset of metabolism-related proteins during type-I interferon responses.

KLF10/CBS increases the sensitivity of gastric carcinoma cells to methionine restriction by promoting sulfur transfer pathway.

Gastric cancer metastasis is a major cause of poor prognosis. Our previous research showed that methionine restriction (MR) lowers the invasiveness and motility of gastric carcinoma. In this study, we investigated the particular mechanisms of MR on gastric carcinoma metastasis. In vitro, gastric carcinoma cells (AGS, SNU-5, MKN7, KATO III, SNU-1, and MKN45) were grown in an MR medium for 24 h. In vivo, BALB/c mice were given a methionine-free (Met-) diet. Transwell assays were used to investigate cell invasion and migration. The amounts of Krüppel like factor 10 (KLF10) and cystathionine ß-synthase (CBS) were determined using quantitative real-time PCR and Western blot. To determine the relationship between KLF10 and CBS, chromatin immunoprecipitation and a dual-luciferase reporter experiment were used. Hematoxylin-eosin staining was used to detect lung metastasis. Liquid chromatography-mass spectrometry was used to determine cystathionine content. MR therapy had varying effects on the invasion and migration of gastric carcinoma cells AGS, SNU-5, MKN7, KATO III, SNU-1, and MKN45. KLF10 was highly expressed in AGS cells but poorly expressed in KATO III cells. KLF10 improved MR's ability to prevent gastric carcinoma cell invasion and migration. In addition, KLF10 may interact with CBS, facilitating transcription. Further detection revealed that inhibiting the KLF10/CBS-mediated trans-sulfur pathway lowered Met-'s inhibitory effect on lung metastasis development. KLF10 transcription activated CBS, accelerated the trans-sulfur pathway, and increased gastric carcinoma cells' susceptibility to MR.

IFNÉ£ but not IFNα increases recognition of insulin defective ribosomal product-derived antigen to amplify islet autoimmunity.

AIMS/HYPOTHESIS: The inflammatory milieu characteristic of insulitis affects translation fidelity and generates defective ribosomal products (DRiPs) that participate in autoimmune beta cell destruction in type 1 diabetes. Here, we studied the role of early innate cytokines (IFNα) and late immune adaptive events (IFNÉ£) in insulin DRiP-derived peptide presentation to diabetogenic CD8+ T cells. METHODS: Single-cell transcriptomics of human pancreatic islets was used to study the composition of the (immuno)proteasome. Specific inhibition of the immunoproteasome catalytic subunits was achieved using siRNA, and antigenic peptide presentation at the cell surface of the human beta cell line EndoC-ßH1 was monitored using peptide-specific CD8 T cells. RESULTS: We found that IFNγ induces the expression of the PSMB10 transcript encoding the ß2i catalytic subunit of the immunoproteasome in endocrine beta cells, revealing a critical role in insulin DRiP-derived peptide presentation to T cells. Moreover, we showed that PSMB10 is upregulated in a beta cell subset that is preferentially destroyed in the pancreases of individuals with type 1 diabetes. CONCLUSIONS/INTERPRETATION: Our data highlight the role of the degradation machinery in beta cell immunogenicity and emphasise the need for evaluation of targeted immunoproteasome inhibitors to limit beta cell destruction in type 1 diabetes. DATA AVAILABILITY: The single-cell RNA-seq dataset is available from the Gene Expression Omnibus (GEO) using the accession number GSE218316 ( https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE218316 ).

STUB1 is targeted by the SUMO-interacting motif of EBNA1 to maintain Epstein-Barr Virus latency.

Latent Epstein-Barr virus (EBV) infection is strongly associated with several malignancies, including B-cell lymphomas and epithelial tumors. EBNA1 is a key antigen expressed in all EBV-associated tumors during latency that is required for maintenance of the EBV episome DNA and the regulation of viral gene transcription. However, the mechanism utilized by EBV to maintain latent infection at the levels of posttranslational regulation remains largely unclear. Here, we report that EBNA1 contains two SUMO-interacting motifs (SIM2 and SIM3), and mutation of SIM2, but not SIM3, dramatically disrupts the EBNA1 dimerization, while SIM3 contributes to the polySUMO2 modification of EBNA1 at lysine 477 in vitro. Proteomic and immunoprecipitation analyses further reveal that the SIM3 motif is required for the EBNA1-mediated inhibitory effects on SUMO2-modified STUB1, SUMO2-mediated degradation of USP7, and SUMO1-modified KAP1. Deletion of the EBNASIM motif leads to functional loss of both EBNA1-mediated viral episome maintenance and lytic gene silencing. Importantly, hypoxic stress induces the SUMO2 modification of EBNA1, and in turn the dissociation of EBNA1 with STUB1, KAP1 and USP7 to increase the SUMO1 modification of both STUB1 and KAP1 for reactivation of lytic replication. Therefore, the EBNA1SIM motif plays an essential role in EBV latency and is a potential therapeutic target against EBV-associated cancers.

Immunohistochemical basigin expression level in thyroid cancer tissues.

BACKGROUND: Thyroid cancer (TC) is the most common endocrine malignancy; basigin (also known as BSG) plays a crucial role in tumor cell invasion, metastasis, and angiogenesis. This study was designed to identify the change of BSG expression in TC and its possible potential mechanism. METHODS: The BSG expression levels in TC were demonstrated using data collected from in-house immunohistochemical (IHC), RNA-sequencing (RNA-seq), microarrays, and literatures. Integrated analysis was performed to determined BSG expression levels in TC comprehensively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed with the integration of BSG co-expressed genes and differentially expressed genes (DEGs) in TC tissues to explore the potential mechanisms of BSG in TC. RESULTS: The protein expression level of BSG was significantly higher in TC cases based on the IHC experiments. In addition, the combined SMD for BSG expression was 0.39 (p < 0.0001), the diagnostic odds ratio was 3.69, and the AUC of the sROC curve was 0.6986 using 1182 TC cases and 437 non-cancerous cases from 17 independent datasets. Furthermore, BSG co-expressed genes tended to be enriched in gene terms of the extracellular matrix (ECM), cell adhesion, and cell-cell interactions. The expression levels of nine hub BSG co-expressed genes were markedly upregulated in TC cases. CONCLUSION: BSG expression levels were closely correlated with the progression of TC and may affect the signals of the ECM, cell adhesion, and cell-cell interactions.

Rapid Covalent-Probe Discovery by Electrophile-Fragment Screening.

Covalent probes can display unmatched potency, selectivity, and duration of action; however, their discovery is challenging. In principle, fragments that can irreversibly bind their target can overcome the low affinity that limits reversible fragment screening, but such electrophilic fragments were considered nonselective and were rarely screened. We hypothesized that mild electrophiles might overcome the selectivity challenge and constructed a library of 993 mildly electrophilic fragments. We characterized this library by a new high-throughput thiol-reactivity assay and screened them against 10 cysteine-containing proteins. Highly reactive and promiscuous fragments were rare and could be easily eliminated. In contrast, we found hits for most targets. Combining our approach with high-throughput crystallography allowed rapid progression to potent and selective probes for two enzymes, the deubiquitinase OTUB2 and the pyrophosphatase NUDT7. No inhibitors were previously known for either. This study highlights the potential of electrophile-fragment screening as a practical and efficient tool for covalent-ligand discovery.

Total chemical synthesis of murine ISG15 and an activity-based probe with physiological binding properties.

The linear synthesis of the N-terminal domain of mISG15 has been developed which enables the synthesis of full-length mISG15 and the activity-based probe Rho-mISG15-PA via native chemical ligation. Pilot experiments showed that the synthetic proteins were properly folded and recognized by endogenous enzymes. Our synthesis strategy allows the generation of other mISG15-based probes and reagents that can accelerate the research in this field.

Manipulation of ubiquitin/SUMO pathways in human herpesviruses infection.

Post-translational modification of proteins with ubiquitin/small ubiquitin-like modifier (SUMO) molecules triggers multiple signaling pathways that are critical for many aspects of cellular physiology. Given that viruses hijack the biosynthetic and degradative systems of their host, it is not surprising that viruses encode proteins to manipulate the host's cellular machinery for ubiquitin/SUMO modification at multiple levels. Infection with a herpesvirus, among the most ubiquitous human DNA viruses, has been linked to many human diseases, including cancers. The interplay between human herpesviruses and the ubiquitylation/SUMOylation modification system has been extensively investigated in the past decade. In this review, we present an overview of recent advances to address how the ubiquitin/SUMO-modified system alters the latency and lytic replication of herpesvirus and how herpesviruses usurp the ubiquitin/SUMO pathways against the host's intrinsic and innate immune response to favor their pathogenesis.

Proteomic profiling identifies the SIM-associated complex of KSHV-encoded LANA.

The Kaposi's sarcoma-associated herpesvirus (KSHV) encoded latent nuclear antigen latency-associated nuclear antigen (LANA) plays an essential role in viral episome maintenance. LANA also contributes to DNA replication and tumorigenesis during latency. Recent studies suggested that LANA was involved in regulation of SUMOylation, which results in chromatin silencing. To examine the pleiotropic effects of LANA protein on host cell gene expression, we utilized MS analysis to identify cellular proteins associated with the small ubiquitin related modifier (SUMO) interacting motif of LANA (LANA(SIM)). In addition to the six bands identified as substantially associated with LANA(SIM), 151 proteins were positively identified by MS/MS analysis. Compared with previous proteomic analysis of the N- and C-truncated mutants of LANA (LANA(NC)), our results revealed that a complex of specific proteins with relatively high SUMOylation and SIM motifs is associated with LANA(SIM). Intriguingly, consistent with our previous report that identified KAP1 as a key component, the in vitro SUMO-2-modified isoform has a substantially higher affinity with LANA(SIM) than the SUMO-1-modified isoform. Moreover, via cluster and pathway analysis, we proposed a hypothetical model for the LANA(SIM) regulatory circuit involving aberrant SUMOylation of cell cycle (particular mitotic), DNA unwinding and replication, and pre-mRNA/mRNA processing related proteins. This study provides a SUMOylated and non-SUMOylated proteome profile of LANA(SIM) -associated complex and facilitates our understanding that viral-mediated gene regulation through SUMOylation is important for Kaposi's sarcoma-associated herpesvirus persistence and pathogenesis.

The relationship between periodontal disease and gastric cancer: A bidirectional Mendelian randomization study.

BACKGROUND: Previous observational studies have suggested a possible association between periodontal disease and gastric cancer (GC); however, a causal relationship has not yet been established. This study aimed to explore the causal relationship between the 2 through a 2-sample bidirectional Mendelian randomization (MR) study. METHODS: Genome-wide association studies (GWAS) summary statistics were obtained from publicly available GWAS and relevant databases. Two-sample bidirectional MR analysis was conducted to investigate the causal relationship between periodontal disease and GC using the inverse-variance weighted (IVW) method selected as the primary analytical approach. Cochran Q test, MR-PRESSO, MR-pleiotropy, and leave-one-out analyses were performed to assess heterogeneity, pleiotropy, and sensitivity. RESULTS: In European ancestry, IVW analysis revealed no causal relationship between periodontal disease and GC (OR = 1.873; 95% CI [4.788e-10, 7.323e + 09]; P = .956), or between loose teeth and GC (OR = 1.064; 95% CI [0.708, 1.598]; P = .765). In East Asian ancestry, there was no causal relationship between periodontitis and GC according to IVW (OR = 0.948; 95% CI [0.886, 1.015]; P = .126). Conversely, according to the results of the IVW analysis, there was no causal relationship between GC and periodontal disease, regardless of European or East Asian ancestry. Furthermore, there was no heterogeneity or pleiotropy in the causal relationships between these variables (all P > .05), suggesting a certain level of reliability in our results. CONCLUSION: Within the limitations of this MR study, we found no mutual causal relationship between periodontal disease and GC. This finding can prevent overtreatment by clinical physicians and alleviate the psychological burden on patients.

Preoperative blood markers and intra-abdominal infection after colorectal cancer resection.

BACKGROUND: Colorectal cancer (CRC) has one of the highest morbidity and mortality rates among digestive tract tumors. Intra-abdominal infection (IAI) is a common postoperative complication that affects the clinical outcomes of patients with CRC and hinders their rehabilitation process. However, the factors influencing abdominal infection after CRC surgery remain unclear; further, prediction models are rarely used to analyze preoperative laboratory indicators and postoperative complications. AIM: To explore the predictive value of preoperative blood markers for IAI after radical resection of CRC. METHODS: The data of 80 patients who underwent radical resection of CRC in the Anorectal Surgery Department of Suzhou Hospital affiliated with Anhui Medical University were analyzed. These patients were categorized into IAI (n = 15) and non-IAI groups (n = 65) based on whether IAI occurred. Influencing factors were compared; general data and laboratory indices of both groups were identified. The relationship between the indicators was assessed. Further, a nomogram prediction model was developed and evaluated; its utility and clinical applicability were assessed. RESULTS: The risk factors for IAI after radical resection of CRC were neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and carcinoembryonic antigen (CEA) levels. NLR was correlated with PLR and SII (r = 0.604, 0.925, and 0.305, respectively), while PLR was correlated with SII (r = 0.787). The nomogram prediction model demonstrated an area under the curve of 0.968 [95% confidence interval (CI): 0.948-0.988] in the training set (n = 60) and 0.926 (95%CI: 0.906-0.980) in the validation set (n = 20). The average absolute errors of the calibration curves for the training and validation sets were 0.032 and 0.048, respectively, indicating a good model fit. The decision curve analysis curves demonstrated high net income above the 5% threshold, indicating the clinical practicality of the model. CONCLUSION: The nomogram model constructed using NLR, PLR, SII, and CEA levels had good accuracy and reliability in predicting IAI after radical resection of CRC, potentially aiding clinical treatment decision-making.

Lower class competence stereotypes of the upper class increase class conflict: mediation by intergroup envy and moderation by upward social mobility belief.

Background: With increasing gaps between the rich and poor, potential risk factors for class conflict have attracted increasing attention from researchers. Although cognitive factors are known to be significant predictors of class-conflict behavior, limited attention has been paid to competence stereotypes of the upper class. When considering economic inequality, people pay more attention to competence stereotypes of the upper class, which may have adverse effects. This study aimed to investigate the relationship between competence stereotypes held by the lower class about the upper class and class conflict, and to test the mediating role of intergroup envy in this relationship and the moderating role of upward social mobility belief. Methods: Data were collected from a convenience sample from a comprehensive university in China. Based on scores on subjective and objective class scales, 284 lower-class college students (103 males and 181 females) aged 18-24 were selected to participate (both their subjective and objective scores were lower than 3 points). Their endorsement of upper-class competence stereotypes, intergroup envy, upward social mobility beliefs, and class conflict were measured using a well-validated self-report questionnaire. Results: The main data were analyzed using correlation analysis, the SPSS macro PROCESS (Model 7), and simple slope analysis. The results show a significant positive correlation between competence stereotypes held by lower-class college students toward the higher class and class conflict, and this connection was mediated by intergroup envy. Moreover, the indirect effect of intergroup envy on this link was moderated by upward social mobility beliefs; this effect was stronger for college students with lower upward social mobility beliefs. Conclusion: This study broadens our understanding of how and when competence stereotypes among the lower class concerning the upper class are related to class conflict. Researchers and policymakers should pay special attention to competence stereotypes of the upper class, especially intergroup envy and class conflict among lower-class individuals with lower levels of upward social mobility beliefs.

A monoclonal antibody that recognizes a unique 13-residue epitope in the cytoplasmic tail of HLA-E.

The Class I MHC molecule (MHC-I) HLA-E presents peptides that are derived from the signal sequences, either those of other MHC-I products, or of viral type I membrane glycoproteins. Monoclonal antibodies with proven specificity for HLA-E, and with no cross-reactions with other MHC-I products, have yet to be described. To obtain anti-HLA-E-specific antibodies suitable for a range of applications, we generated monoclonal antibodies against a unique feature of HLA-E: its cytoplasmic tail. We created an immunogen by performing an enzymatically catalyzed transpeptidation reaction to obtain a fusion of the cytoplasmic tail of HLA-E with a nanobody that recognizes murine Class II MHC (MHC-II) products. We obtained a mouse monoclonal antibody that recognizes a 13-residue stretch in the HLA-E cytoplasmic tail. We cloned the genes that encode this antibody in expression vectors to place an LPETG sortase recognition motif at the C-terminus of the heavy and light chains. This arrangement allows the site-specific installation of fluorophores or biotin at these C-termini. The resulting immunoglobulin preparations, labeled with 4 equivalents of a fluorescent or biotinylated payload of choice, can then be used for direct immunofluorescence or detection of the tag by fluorescence or by streptavidin-based methods. We also show that the 13-residue sequence can serve as an epitope tag, independent of the site of its placement within a protein's sequence. The antibody can be used diagnostically to stain for HLA-E on patient tumor samples, it can be used as an antibody-epitope tag for extracellular proteins, and it enables research into the unique role of the cytoplasmic tail of HLA-E.

The optimal atropine concentration for myopia control in Chinese children: a systematic review and network Meta-analysis.

AIM: To figure out whether various atropine dosages may slow the progression of myopia in Chinese kids and teenagers and to determine the optimal atropine concentration for effectively slowing the progression of myopia. METHODS: A systematic search was conducted across the Cochrane Library, PubMed, Web of Science, EMBASE, CNKI, CBM, VIP, and Wanfang database, encompassing literature on slowing progression of myopia with varying atropine concentrations from database inception to January 17, 2024. Data extraction and quality assessment were performed, and a network Meta-analysis was executed using Stata version 14.0 Software. Results were visually represented through graphs. RESULTS: Fourteen papers comprising 2475 cases were included; five different concentrations of atropine solution were used. The network Meta-analysis, along with the surface under the cumulative ranking curve (SUCRA), showed that 1% atropine (100%)>0.05% atropine (74.9%) >0.025% atropine (51.6%)>0.02% atropine (47.9%)>0.01% atropine (25.6%)>control in refraction change and 1% atropine (98.7%)>0.05% atropine (70.4%)>0.02% atropine (61.4%)>0.025% atropine (42%)>0.01% atropine (27.4%)>control in axial length (AL) change. CONCLUSION: In Chinese children and teenagers, the five various concentrations of atropine can reduce the progression of myopia. Although the network Meta-analysis showed that 1% atropine is the best one for controlling refraction and AL change, there is a high incidence of adverse effects with the use of 1% atropine. Therefore, we suggest that 0.05% atropine is optimal for Chinese children to slow myopia progression.

Differential response to copper stress in the reproductive resources and allocation of metallophyte Kummerowia stipulacea.

Abundant seed production is a key life history trait for plant to maintain the stability of the whole population in adverse environments such as heavy metal contaminated mine area. In the current studies, we hypothesize that mine (metallicolous) populations of metallophytes have formed specialized reproductive strategies to adapt themselves to the heavy metal contaminated habitats, and differ from normal (non-metallicolous) populations in reproductive allocation. To test this hypothesis, the differences in reproductive resources and reproductive allocation between the copper mine and non-copper mine populations of pseudo-metallophyte Kummerowia stipulacea were comparatively examined under controlled Cu exposure experiments. Compared to non-copper mine population, copper mine population shows an increased seed output and larger reproductive effort under Cu stress. The increase of reproductive allocation in metallicolous population depends on not only seed size but also seed number per plant. The plants of metallicolous population increase allocation to the reproductive organs at the expense of a curtailment of allocation to vegetative traits, resulting in plants with shorter height and fewer branch numbers. There is little evidence displaying effect of root nodule on the reproductive resources and allocation. In addition, plants in metallicolous population reduce the transfer of Cu from roots to aboveground parts. These data suggest that plants of metallicolous population tend to invest more resources to reproductive output and increase their reproductive allocation in the adaptive evolution to Cu-enriched mine soils.

VPS72, a member of VPS protein family, can be used as a new prognostic marker for hepatocellular carcinoma.

BACKGROUND: Vacuolar protein sorting (VPS) plays a crucial role in intracellular molecular transport between organelles. However, studies have indicated a correlation between VPSs and tumorigenesis and the development of several cancers. Nevertheless, the association between VPSs and hepatocellular carcinoma (HCC) remains unclear. METHODS: By analyzing databases such as The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC), we investigated the differences in VPSs expression between normal tissue and HCC transcriptomes. Furthermore, we examined the relationship between VPSs expression and overall survival (OS) in patients with HCC. Univariate and multivariate Cox analyses were employed to assess the prognostic value of VPS72 as an independent factor, and the correlation between VPS72 and the tumor immune microenvironment was also analyzed. RESULTS: We observed significant overexpression of 28 VPSs in HCC tissues compared to normal tissues. The mRNA expression of VPSs displayed a negative correlation with OS, while exhibiting a positive correlation with tumor grade and stage. Additionally, both univariate and multivariate Cox analyses identified VPS72 as a potential independent risk factor for HCC prognosis. Overexpression of VPS72 demonstrated a positive correlation with various clinicopathological factors associated with poor prognosis, as well as the infiltration levels of immune cells. CONCLUSION: Therefore, our research shows that VPSs participate in HCC occurrence and development, especially VPS72, which may act as a potential target for HCC treatment and prognosis biomarker.

Angiopoietin4 (ANGPT4) expression and potential mechanisms in carcinogenesis: current achievements and perspectives.

Angiopoietin4(ANGPT4) which plays a significant role in endothelial cell proliferation, survival, angiogenesis and expansion in tumors and other pathological states is a significant regulator of tumor angiogenesis. ANGPT4 expression is enhanced in many cancer cells. For example, the overexpression of ANGPT4 promotes the formation, development and progress of lung adenocarcinoma, glioblastoma and ovarian cancer. Related studies show that ANGPT4 encourages the proliferation, survival and invasion of tumor cells, while promoting the expansion of the tumor vascular system and affecting the tumor immune microenvironment. ANGPT4 can also promote carcinogenesis by affecting the ERK1/2, PI3K/AKT and other signal pathways downstream of tyrosine kinase with immunoglobulin-like and EGF-like domains 2(TIE2) and TIE2. Therefore, ANGPT4 may be a potential and significant biomarker for predicting malignant tumor progression and adverse outcomes. In addition, inhibition of ANGPT4 may be a meaningful cancer treatment. This paper reviews the latest research results of ANGPT4 in preclinical research, and emphasizes its role in carcinogenesis. Additional research on the carcinogenic function of ANGPT4 could provide new insights into cancer biology and novel methods for cancer diagnosis and treatment.

Potential Therapeutic Effects of Policosanol from Insect Wax on Caenorhabditis elegans Models of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. The standard treatments for PD focus on symptom relief rather than attempting to address the underlying degenerative processes completely. This study aimed to evaluate the potential therapeutic effects of policosanol derived from insect wax (PIW) by investigating improvements in disease symptoms represented in Caenorhabditis elegans models of PD. For our assessments, we used the following three models: NL5901, which is a transgenic model for α-synuclein aggregation; wild-type N2 induced with 6-hydroxydopamine (6-OHDA); and 6-OHDA-induced BZ555 as a model for loss of dopaminergic neurons (DNs). Specifically, we examined the effects of PIW treatment on α-synuclein aggregation, the loss of DNs, lipid abundance, and the lifespan of treated organisms. Further, we examined treatment-related changes in the levels of reactive oxygen species (ROS), malondialdehyde (MDA), adenosine triphosphate (ATP), glutathione S-transferase (GST), and superoxide dismutase (SOD), as well as the mRNA production profiles of relevant genes. A 10 µg/mL dose of PIW reduced the aggregation of α-synuclein in NL5901 and suppressed the loss of DNs in 6-OHDA-induced BZ555. Overall, PIW treatment decreased ROS and MDA levels, restored lipid abundance, and prolonged the lifespans of worms in all the three models, which may be associated with changes in the expression profiles of genes related to cell survival and oxidative stress response pathways. Our findings show that PIW alleviated the symptoms of PD in these models, possibly by regulating the stress responses initiated by injuries such as α-synuclein aggregation or 6-OHDA treatment.

Two-point fixation enhanced the outcome of laparoscopy-assisted ventriculoperitoneal shunt in adult patients with hydrocephalus: a retrospective study.

Objective: In patients with hydrocephalus, laparoscopy significantly improved ventriculoperitoneal shunt (VPS) outcomes. However, abdominal complications still occur, which require revision surgeries. In this study, we aimed to examine whether laparoscopy-assisted VPS with two-point fixation (LAVPS-TPF) has better outcomes than those of VPS (open-VPS) and laparoscopy-assisted VPS with no fixation (LAVPS-NF). Methods: We retrospectively reviewed clinical records of 105 open-VPS, 40 LAVPS-NF, and 49 LAVPS-TPF cases from 2015 to 2020. Data including body mass index, etiology, abdominal surgery history, Glasgow coma scale (GCS), operation time, in-hospital days, shunt failure, complications, and modified Rankin scores were analyzed, as well as subgroups of patients with history of abdominal surgery, GCS scores, and revision surgeries. Results: The LAVPS-TPF group demonstrated decreased shunt failure rates at 12 months (2.04%) compared to those of the open-VPS group (14.29%, P = 0.020) and reduced abdominal shunt-related complications (P = 0.004 vs. open-VPS and LAVPS-NF) and shunt revisions. In the LAVPS-TPF group with abdominal history (n = 51), 12-month shunt failure rates (P = 0.020 vs. open-VS), repair frequency (P = 0.020 vs. open-VS), and abdominal complications (P = 0.003 and 0.006 vs. open-VS and LAVPS-NF) were reduced. In the LAVPS-TPF group with GCS scores of 13-15 (n = 152), shunt failure rates at 12 months, abdominal complications, and revision frequency were decreased (P < 0.05 vs. other groups). Compared to the LAVPS-NF group, neurological complications were also reduced (P = 0.001). Among revision surgeries (n = 28), fixed shunts resulted in improved shunt survival rates at 12 months, reduced abdominal complications, and secondary revisions (P < 0.05). Moreover, a more optimal recovery without neurological sequelae was achieved by shunt fixation than that by LAVPS-NF (P < 0.01). Conclusions: LAVPS-TPF significantly improved shunt survival rates at 12 months and reduced the incidence of abdominal shunt-related complications compared to open-VPS and LAVPS-NF, especially in patients with history of abdominal surgery, higher GCS scores, and revision surgeries. However, further studies are required to confirm these benefits.