Activity Limitations and Depression Among Middle-Aged and Older Adults in China: The Moderating Impact of Assistance Adequacy.

This study aimed to examine the risk and protective factors associated with depression in middle-aged and older Chinese adults with activity limitations. Data were obtained from the 2018 Wave 4 Survey of the China Health and Retirement Longitudinal Study. In the logistic regression analysis, health and functioning, losing a child, and a perceived lack of future assistance with daily activities increased the odds of depression. Conversely, receiving adequate assistance with daily activities lessened the depressive impacts of activity limitations, as indicated by a significant interaction effect. Enhanced long-term support for individuals with disabilities is necessary to improve mental health.

Metabolomic and chemometric analyses of St. John's wort and related Asian Hypericum species linked to bioactivity.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants in the genus Hypericum (Hypericaceae), include more than 500 species worldwide, and many are valued for their medicinal properties, and are used as traditional herbal medicines. However, only H. perforatum is officially recognized as herbal drug in several pharmacopoeias, and used as an antidepressant clinically. Hypericum perforatum had been used as an herbal medicine since the Han Dynasty (206 B.C. -220 A.D.) in China. It taxonomically belongs to the section Hypericum in the genus Hypericum. There are about 42 species in the section Hypericum, with six species occurring in China. All six are recorded as traditional herbal medicines for treating aliments, including hepatitis, malaria, traumatic hemorrhage, irregular menstruation, wounds, and bruises. AIM OF THE STUDY: The study aimed to characterize the chemical profiles of five phylogenetically related Hypericum species, and compare their metabolites with three H. perforatum products. Informed by ethnobotanical use, the extracts prepared from the five species were further investigated into anticancer, anti-inflammatory and antiplasmodial activity. This study tested the hypothesis that systematic metabolomic and bioactivity characterization of species in section Hypericum will help to validate their phytotherapeutic use and reveal potential drug lead compounds. MATERIALS AND METHODS: Targeted and non-targeted metabolic analyses coupled with chemometrics were conducted on H. perforatum and four medicinal species, H. attenuatum, H. enshiense, H. erectum, and H. faberi, native to China from section Hypericum. UPLC-QTOF-MS/MS and UPLC-TQD-MS/MS were used for non-targeted and targeted metabolic analyses, respectively. Cytotoxicity bioassays on four cancer cell lines, anti-inflammation tests and anti-plasmodial activity on Plasmodium falciparum 3D7, selected based on traditional medicinal use, were evaluated on extracts from Hypericum species. Progenesis QI and EZinfo were used for chemometrics analysis to link the chemical profile and bioassay activity to aid in the identification of bioactive compounds. RESULTS: In total, 58 compounds were identified from the five species, including compounds with well-characterized bioactivity. Hypericum attenuatum, H. erectum, and H. perforatum, displayed the highest cytotoxicity, and contain the cytotoxic compounds petiolin A, prolificin A, and hypercohin G, respectively. Hypericum faberi and H. perforatum showed the highest anti-inflammatory activity, with pseudohypericin, quercetin and chlorogenic acid being observed at higher concentrations. Hypericum perforatum and H. erectum showed anti-plasmodial activity, with higher hyperforin and xanthones in these species that may account for the anti-plasmodial activity. CONCLUSIONS: This study characterized the chemical differences among five Hypericum species using metabolomics. These ethnomedically important species were tested for their biological activities in three distinct in vitro assays. The ethnobotanical data were useful for identifying bioactive Hypericum species. Hypericum attenuatum, H. erectum and H. faberi are promising phytotherapeutic species, although they are much less studied than H. perforatum, St. John's wort. Combining ethnobotanical surveys with chemometric analyses and bioactivity screening can greatly enhance the discovery of promising active constituents.

Novel role of lncRNAs regulatory network in papillary thyroid cancer.

Papillary thyroid cancer (PTC) is the most common endocrine malignancy. The incidence of PTC has increased annually worldwide. Thus, PTC diagnosis and treatment attract more attention. Noncoding RNAs (lncRNAs) play crucial roles in PTC progression and act as prognostic biomarkers. Moreover, microRNAs (miRNAs) and epithelial-mesenchymal transition (EMT)-associated proteins have potential biomarkers for diagnosing and treating PTC. However, the correlation of lncRNAs with miRNAs and EMT-associated proteins needs further clarification. The present review highlights the recent advances of lncRNAs in PTC. We significantly summarized the two molecular regulatory mechanisms in PTC progress, including lncRNAs-miRNAs-protein signaling axes and lncRNAs-EMT pathways. This review will help our understanding of the association between lncRNAs and PTC and may assist us in evaluating the prognosis for PTC patients. Taken together, targeting the lncRNAs regulatory network has promising applications in diagnosing and treating PTC.

Geriatric nutritional risk index is correlated with islet function but not insulin resistance in elderly patients with type 2 diabetes: A retrospective study.

The geriatric nutritional risk index (GNRI) is a simple nutritional assessment tool that can predict poor prognosis in elderly subjects. The aim of this study was to evaluate the association between GNRI and both islet function and insulin sensitivity in patients with type 2 diabetes mellitus. This research carries significant implications for the integrated treatment and nutritional management of this patient population. A total of 173 patients with type 2 diabetes mellitus, aged 60 years or older, who were hospitalized in the Endocrinology Department at Hebei General Hospital from February 2018 to June 2021, were selected as the research subjects. These subjects were divided into 4 groups according to the quartile of their GNRI values: T1 (GNRI < 99.4, n = 43), T2 (99.4 ≤ GNRI < 103, n = 43), T3 (103 ≤ GNRI < 106.3, n = 43), and T4 (GNRI ≥ 106.3, n = 44). Glucose, insulin, and C-peptide concentrations were tested at 0, 30, 60, 120, and 180 minutes during a 75 g oral glucose tolerance test. The homeostasis model assessment for insulin resistance and the homeostasis model assessment for ß cell function index were calculated. As the GNRI value increased, the levels of total protein, albumin, hemoglobin, alanine transaminase, aspartate aminotransferase, and 25-hydroxyvitamin D increased significantly. The area under the curve for blood glucose decreased significantly across the 4 groups, while the AUCs for insulin and C-peptide showed an overall increasing trend. ß Cell function index increased significantly with the increase of GNRI; meanwhile, both the early-phase insulin secretion index and the late-phase insulin secretion index increased significantly. Although there was an increasing trend, homeostasis model assessment for insulin resistance did not change significantly among the 4 groups. This study indicates that elderly type 2 diabetes patients with higher nutritional risk have worse islet function, while insulin sensitivity is not associated with nutritional risk.

Transcriptome-Based Identification of the SaR2R3-MYB Gene Family in Sophora alopecuroides and Function Analysis of SaR2R3-MYB15 in Salt Stress Tolerance.

As one of the most prominent gene families, R2R3-MYB transcription factors significantly regulate biochemical and physiological processes under salt stress. However, in Sophora alopecuroides, a perennial herb known for its exceptional saline alkali resistance, the comprehensive identification and characterization of SaR2R3-MYB genes and their potential functions in response to salt stress have yet to be determined. We investigated the expression profiles and biological functions of SaR2R3-MYB transcription factors in response to salt stress, utilizing a transcriptome-wide mining method. Our analysis identified 28 SaR2R3-MYB transcription factors, all sharing a highly conserved R2R3 domain, which were further divided into 28 subgroups through phylogenetic analysis. Some SaR2R3-MYB transcription factors showed induction under salt stress, with SaR2R3-MYB15 emerging as a potential regulator based on analysis of the protein-protein interaction network. Validation revealed the transcriptional activity and nuclear localization of SaR2R3-MYB15. Remarkably, overexpression of SaR2R3-MYB15 in transgenic plants could increase the activity of antioxidant enzymes and the accumulation of proline but decrease the content of malondialdehyde (MDA), compared with wild-type plants. Moreover, several salt stress-related genes showed higher expression levels in transgenic plants, implying their potential to enhance salt tolerance. Our findings shed light on the role of SaR2R3-MYB genes in salt tolerance in S. alopecuroides.

A review on nocturnal surface ozone enhancement: Characterization, formation causes, and atmospheric chemical effects.

In recent years, the frequent occurrence of nocturnal background ozone enhancement (A gradually increasing trend in the long-term change of nocturnal ozone concentration, [NBOE]) and nocturnal ozone enhancement (the presence of a nocturnal ozone peak and high nocturnal ozone value, [NOE]) have attracted extensive attention in the academic community. NBOE and NOE impact atmospheric chemical processes, and higher nocturnal ozone concentrations adversely affect human health and biological growth. Therefore, we reviewed the research history of NBOE and NOE, provided an overview of research on NBOE, and summarized the spatiotemporal distribution characteristics of NOE. According to the available observations, the frequency of NOE in a long-time series (i.e., more than one year) from 2005 to 2020 generally ranges between 15 % and 50 %. Compared to other nations, China has a higher nocturnal ozone peak. In most NOE events, the magnitude of ozone increase (ΔO3/Δt) ranges from 5 to 20 ppb, and NOE events occur more frequently during midnight. In addition, we described the current international-level understanding of the causes of NOE and the impact of NOE on nighttime and next-day atmospheric chemical processes. Future research should not only enhance the quantitative analysis of the causal factors of NBOE and NOE, but also prioritize exploring how NBOE and NOE influence secondary pollutant production, human health, and biological growth. Finally, attention should be paid to the influence of NBOE and NOE on the formulation of synergistic control policies for PM2.5 and ozone.

Artificial neural network for deciphering the structural transformation of condensed ZnO by extended x-ray absorption fine structure spectroscopy.

Pressure-induced structural phase transitions play a pivotal role in unlocking novel material functionalities and facilitating innovations in materials science. Nonetheless, unveiling the mechanisms of densification, which relies heavily on precise and comprehensive structural analysis, remains a challenge. Herein, we investigated the archetypalB4 →B1 phase transition pathway in ZnO by combining x-ray absorption fine structure (XAFS) spectroscopy with machine learning. Specifically, we developed an artificial neural network (NN) to decipher the extended-XAFS spectra by reconstructing the partial radial distribution functions of Zn-O/Zn pairs. This provided us with access to the evolution of the structural statistics for all the coordination shells in condensed ZnO, enabling us to accurately track the changes in the internal structural parameteruand the anharmonic effect. We observed a clear decrease inuand an increased anharmonicity near the onset of theB4 →B1 phase transition, indicating a preference for the iT phase as the intermediate state to initiate the phase transition that can arise from the softening of shear phonon modes. This study suggests that NN-based approach can facilitate a more comprehensive and efficient interpretation of XAFS under complexin-situconditions, which paves the way for highly automated data processing pipelines for high-throughput and real-time characterizations in next-generation synchrotron photon sources.

Dynamic monitoring of neutrophil/lymphocyte ratio, APACHE II score, and SOFA score predict prognosis and drug resistance in patients with Acinetobacter baumannii-calcoaceticus complex bloodstream infection: a single-center retrospective study.

Objective: This study aimed to evaluate the clinical value of dynamic monitoring of neutrophil/lymphocyte ratio (NLR), APACHE II (Acute Physiology and Chronic Health Evaluation II) score, and Sequential Organ Failure Assessment (SOFA) score in predicting 28-day prognosis and drug resistance in patients with bloodstream infection with Acinetobacter baumannii-calcoaceticus complex (Abc complex). Patients and methods: In this research, individuals admitted to Tianjin Medical University General Hospital from January 2017 to March 2023 with bloodstream infections and a minimum of one Abc complex positive blood culture were chosen. The risk factors for the 28-day prognosis and drug resistance were analyzed using logistic regression. The NLR, APACHE II score, and SOFA score were evaluated for predicting 28-day prognosis and drug resistance using an ROC curve analysis. The data were analyzed using R Studio to find correlations and conduct survival analysis with the Kaplan-Meier method. Results: The final statistical analysis included a total of 129 patients with bloodstream infections caused by Abc complex. Independent risk factors predicting mortality within 28 days were identified as follows: the SOFA score and APACHE II scores at 24 h, and APACHE II scores at 72 h after the onset of blood infection (p < 0.05). NLR, SOFA score, and APACHE II score did not predict drug resistance. Patients with Carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (CRAB) had shorter survival times than those with carbapenem-sensitive strains (40.77 days vs. 47.65 days, respectively, p = 0.0032). Conclusion: The prognosis of Abc complex bloodstream infection is affected by both SOFA and APACHE II scores. Both scoring systems have similar prognostic values at different time points after infection, but for computational convenience, it is recommended to use the SOFA score. NLR exhibits limited effectiveness in predicting mortality within 28 days. Carbapenem-resistant individuals with Abc complex experience significantly reduced survival time. None of the three factors-SOFA score, APACHE II score, and NLR-can early predict the occurrence of CRAB infections effectively.

Isolation and absolute configuration of alkylpyridine alkaloids from the marine sponge Hippospongia lachne.

Marine sponges are well known as prolific producers of structurally diverse molecules with valuable pharmacological potential. As part of our ongoing program to discover bioactive compounds from marine sponges collected from the Xisha Islands in the South China Sea, a chemical study on the specimens of Hippospongia lachne was conducted. As a result, eight undescribed compounds, including four zwitterionic alkylpyridinium salts, hippospondines A-D (1-4), and four 3-alkylpyridine alkaloids, hippospondines E (5), F (6), and (±)-hippospondine G (7), were isolated from the marine sponge H. lachne, together with one known 3-alkylpyridine alkaloid (8). The undescribed structures were elucidated by HRESIMS, NMR, DP4+ and CP3 probability analysis, and the Snatzke's method. Hippospondines A-D (1-4) represent the rare example of inner salt type alkylpyridinium alkaloid with a farnesyl moiety. Compounds 1-3 and 8 were subjected to cytotoxic and lymphocyte proliferation assays. Compound 3 exhibited a weak promotion effect on the ConA-induced T lymphocyte proliferation.

Immunogenicity of an adenovirus-vectored bivalent vaccine against wild type SARS-CoV-2 and Omicron variants in a murine model.

BACKGROUND: The emergence and rapid spread of new mutant strains of SARS-CoV-2 necessitate the development of a new generation vaccine capable of neutralizing a broad range of variants. When the SARS-CoV-2 Omicron variant emerged, individuals in China had already received an inactivated (INA) or a type 5 adenovirus-vectored (Ad5) SARS-CoV-2 vaccine targeting the wild-type virus. We have recently developed a bivalent recombinant type 5 vaccine targeting both the wild-type strain and the Omicron variant (Ad5-nCoV/O). The objectives of this study were to assess the immunogenicity of the bivalent vaccine as a booster against both the wild type and the Omicron variant. METHODS: In the single immunization model, mice received one intramuscular immunization with monovalent or bivalent Ad5-vectored vaccines targeting both wild-type SARS-CoV-2 and Omicron variants. In the prime-boost model, mice were primed intramuscularly with an INA or Ad5-vectored vaccine targeting wild-type SARS-CoV-2, and then boosted intramuscularly or intranasally with heterologous or homologous INA or monovalent or bivalent Ad5-vectored vaccines targeting both wild-type SARS-CoV-2 and Omicron variants. The vaccine-induced antibody responses and cellular immune responses were measured using ELISA, pseudovirus-based neutralization assays, the intracellular cytokine staining (ICS) and ELISpot. RESULTS: Single-dose prime vaccination with the monovalent and bivalent vaccines elicited robust antibody responses and CD4 + and CD8 + cellular responses against the spike protein of WT and Omicron SARS-CoV-2. Both intramuscular and intranasal boost vaccination with the bivalent Ad5-nCoV/O following a prime with INA or Ad5-vectored vaccines induced strong serum neutralization antibody responses to both wild type and Omicron variants. A heterologous prime-boost vaccination elicited greater neutralization antibody responses than a homologous prime-boost vaccination when mice were boosted with Ad5-vectored vaccines following a prime with INA. Intranasal boost also resulted in significant mucosal IgA responses. CONCLUSION: The bivalent vaccine Ad5-nCoV/O exhibited robust immunogenicity, inducing broad-spectrum cross-neutralizing antibodies and cellular immune responses against both wild type and Omicron variants of SARS-CoV-2. The results demonstrated the potential of the bivalent vaccine in addressing the challenges posed by emerging SARS-CoV-2 Omicron variants.

The effect of heterogeneous severe drought on all-cause and cardiovascular mortality in the Northern Rockies and Plains of the United States.

Drought is a distinct and complicated climate hazard that regularly leads to severe economic impacts. Changes in the frequency and occurrence of drought due to anthropogenic climate change can lead to new and unanticipated outcomes. To better prepare for health outcomes, more research is needed to develop methodologies to understand potential consequences. This study suggests a new methodology for assessing the impact of monthly severe drought exposure on mortality in the Northern Rockies and Plains of the United States from 2000 to 2018. A two-stage model with the power prior approach was applied to integrate heterogeneous severe drought pattern and estimate overall risk ratios of all-cause and cardiovascular mortality related to multiple drought indices (the US Drought Monitor, 6- and 12-month Standardized Precipitation-Evapotranspiration Index, 6- and 12 month Evaporative Demand Drought Index). Under severe drought, the risk ratios of all-cause mortality are 1.050 (95 % Cr: 1.031 to 1.071, USDM), 1.041 (95 % Cr: 1.022 to 1.060, 6-SPEI), 1.009 (95 % Cr: 0.989 to 1.031, 12SPEI), 1.045 (95 % Cr: 1.022 to 1.067, 6-EDDI), and 1.035 (95 % Cr: 1.009 to 1.062, 12-EDDI); cardiovascular mortality are 1.057 (95 % Cr: 1.023 to 1.091, USDM), 1.028 (95 % Cr: 0.998 to 1.059, 6-SPEI), 1.005 (95 % Cr: 0.973 to 1.040, 12-SPEI), 1.042 (95 % Cr: 1.005 to 1.080, 6-EDDI), and 1.004 (95 % Cr: 0.959 to 1.049, 12-EDDI). Our results showed that (i) a model with properly accounted for heterogeneous exposure pattern had greater risk ratios if statistically significant; (ii) a mid-term (6-month) severe drought had higher risk ratios compared to longer-term (12-month) drought; and (iii) different severe droughts affect populations in a different way. These results expand the existing knowledge of drought relationship to increasing mortality in the United States. The findings from this study highlight the need for communities and policymakers to establish effective drought-prevention initiatives in this region.

Early life changes in histone landscape protect against age-associated amyloid toxicities through HSF-1-dependent regulation of lipid metabolism.

Transient events during development can exert long-lasting effects on organismal lifespan. Here we demonstrate that exposure of Caenorhabditis elegans to reactive oxygen species during development protects against amyloid-induced proteotoxicity later in life. We show that this protection is initiated by the inactivation of the redox-sensitive H3K4me3-depositing COMPASS complex and conferred by a substantial increase in the heat-shock-independent activity of heat shock factor 1 (HSF-1), a longevity factor known to act predominantly during C. elegans development. We show that depletion of HSF-1 leads to marked rearrangements of the organismal lipid landscape and a significant decrease in mitochondrial ß-oxidation and that both lipid and metabolic changes contribute to the protective effects of HSF-1 against amyloid toxicity. Together, these findings link developmental changes in the histone landscape, HSF-1 activity and lipid metabolism to protection against age-associated amyloid toxicities later in life.

Potentiation of the lateral habenula-ventral tegmental area pathway underlines the susceptibility to depression in mice with chronic pain.

Chronic pain often develops severe mood changes such as depression. However, how chronic pain leads to depression remains elusive and the mechanisms determining individuals' responses to depression are largely unexplored. Here we found that depression-like behaviors could only be observed in 67.9% of mice with chronic neuropathic pain, leaving 32.1% of mice with depression resilience. We determined that the spike discharges of the ventral tegmental area (VTA)-projecting lateral habenula (LHb) glutamatergic (Glu) neurons were sequentially increased in sham, resilient and susceptible mice, which consequently inhibited VTA dopaminergic (DA) neurons through a LHbGlu-VTAGABA-VTADA circuit. Furthermore, the LHbGlu-VTADA excitatory inputs were dampened via GABAB receptors in a pre-synaptic manner. Regulation of LHb-VTA pathway largely affected the development of depressive symptoms caused by chronic pain. Our study thus identifies a pivotal role of the LHb-VTA pathway in coupling chronic pain with depression and highlights the activity-dependent contribution of LHbGlu-to-VTADA inhibition in depressive behavioral regulation.

Research on ozone formation sensitivity based on observational methods: Development history, methodology, and application and prospects in China.

Observation-based method for O3 formation sensitivity research is an important tool to analyze the causes of ground-level O3 pollution, which has broad application potentials in determining the O3 pollution formation mechanism and developing prevention and control strategies. This paper outlined the development history of research on O3 formation sensitivity based on observational methods, described the principle and applicability of the methodology, summarized the relative application results in China and provided recommendations on the prevention and control of O3 pollution in China based on relevant study results, and finally pointed out the shortcomings and future development prospects in this field in China. The overview study showed that the O3 formation sensitivity in some urban areas in China in recent years presented a gradual shifting tendency from the VOC-limited regime to the transition regime or the NOx-limited regime due to the implementation of the O3 precursors emission reduction policies; O3 pollution control strategies and precursor control countermeasures should be formulated based on local conditions and the dynamic control capability of O3 pollution control measures should be improved. There are still some current deficiencies in the study field in China. Therefore, it is recommended that a stereoscopic monitoring network for atmospheric photochemical components should be further constructed and improved; the atmospheric chemical mechanisms should be vigorously developed, and standardized methods for determining the O3 formation sensitivity should be established in China in the near future.

EHBP1 Is Critically Involved in the Dendritic Arbor Formation and Is Coupled to Factors Promoting Actin Filament Formation.

The coordinated action of a plethora of factors is required for the organization and dynamics of membranous structures critically underlying the development and function of cells, organs, and organisms. The evolutionary acquisition of additional amino acid motifs allows for expansion and/or specification of protein functions. We identify a thus far unrecognized motif specific for chordata EHBP1 proteins and demonstrate that this motif is critically required for interaction with syndapin I, an F-BAR domain-containing, membrane-shaping protein predominantly expressed in neurons. Gain-of-function and loss-of-function studies in rat primary hippocampal neurons (of mixed sexes) unraveled that EHBP1 has an important role in neuromorphogenesis. Surprisingly, our analyses uncovered that this newly identified function of EHBP1 did not require the domain responsible for Rab GTPase binding but was strictly dependent on EHBP1's syndapin I binding interface and on the presence of syndapin I in the developing neurons. These findings were underscored by temporally and spatially remarkable overlapping dynamics of EHBP1 and syndapin I at nascent dendritic branch sites. In addition, rescue experiments demonstrated the necessity of two additional EHBP1 domains for dendritic arborization, the C2 and CH domains. Importantly, the additionally uncovered critical involvement of the actin nucleator Cobl in EHBP1 functions suggested that not only static association with F-actin via EHBP1's CH domain is important for dendritic arbor formation but also actin nucleation. Syndapin interactions organize ternary protein complexes composed of EHBP1, syndapin I, and Cobl, and our functional data show that only together these factors give rise to proper cell shape during neuronal development.

A review: Mechanism and prospect of gastrodin in prevention and treatment of T2DM and COVID-19.

Gastrodin is an extract from the dried tuber of the Chinese herb Gastrodia elata (Tian ma), with anti-inflammatory, antioxidant, and antiviral properties. Recent studies have shown that, compared to commonly used diabetes drugs, gastrodin has antidiabetic effects in multiple ways, with characteristics of low cost, high safety, less side effects, protection of ß-cell function, relieving insulin resistance and alleviating multiple complications. In addition, it is confirmed that gastrodin can protect the function of lung and other organs, enhance antiviral activity via upregulating the type I interferon (IFN-I), and inhibit angiotensin II (AngII), a key factor in "cytokine storm" caused by COVID-19. Therefore, we reviewed the effect and mechanism of gastrodin on type 2 diabetes mellitus (T2DM), and speculated other potential mechanisms of gastrodin in alleviating insulin resistance from insulin signal pathway, inflammation, mitochondrial and endoplasmic reticulum and its potential in the prevention and treatment of COVID-19. We hope to provide new direction and treatment strategy for basic research and clinical work: gastrodin is considered as a drug for the prevention and treatment of diabetes and COVID-19.

Machine learning developed a PI3K/Akt pathway-related signature for predicting prognosis and drug sensitivity in ovarian cancer.

BACKGROUND: Ovarian cancer is one of the deadliest malignancies among females, generally having a poor prognosis. The PI3K/Akt pathway plays a vital role in the oncogenesis and progression of many types of cancer. Limited studies have fully clarified the role of PI3K/Akt pathway in the prognosis of ovarian cancer and its correlation with drug sensitivity. METHODS: A prognostic PI3K/Akt pathway related signature (PRS) was constructed with 10 machine learning algorithms using TCGA, GSE14764, GSE26193, GSE26712, GSE63885 and GSE140082 datasets. Gaussian mixture and logistic regression were performed to identify the optimal models for classifying lymphatic and venous invasion. RESULTS: The optimal prognostic PRS developed by Lasso + survivalSVM algorithm acted as an independent risk factor for overall survival (OS) of ovarian cancer patients and had a good performance in evaluating OS rate of ovarian cancer patients. Significant correlation was obtained between PRS-based risk score and Immune score, ESTIMATE score, immune cells and cancer-related hallmarks. Low risk score indicated a lower immune escape score, TIDE score, and higher PD1&CTLA4 immunophenoscore in ovarian cancer. Moreover, PRS-based risk score acted as an indicator for drug sensitivity in the immunotherapy and chemotherapy of ovarian cancer patients. CONCLUSIONS: All in all, our study developed a prognostic PRS showing powerful and good performance in predicting clinical outcome of ovarian cancer patients. PRS could serve as an indicator for drug sensitivity in the chemotherapy and immunotherapy.

Potential regulatory role of the Nrf2/HMGB1/TLR4/NF-κB signaling pathway in lupus nephritis.

OBJECTIVES: Systemic lupus erythematosus is an autoimmune disease that involves multiple organ systems. One of its major complications, lupus nephritis (LN), is associated with a high mortality rate, and children-onset LN have a more severe course and worse prognosis than adults. Oxidative stress and inflammatory responses are involved in LN development and pathogenesis. Thus, this study aimed to explore the role of signaling regulation of the Nrf2/HMGB1/TLR/NF-κB pathway in LN pathogenesis and unravel the expression of TLR4+CXCR4+ plasma cells subset (PCs) in LN. METHODS: C57BL/6 and MRL/lpr mice were divided into four groups: control, model, vector control, and Nrf2 overexpression groups. The vector control and Nrf2 overexpression groups were injected with adenoviral vectors into the kidney in situ. Pathological changes in kidney tissues were observed by hematoxylin-eosin staining. The expression of Nrf2, HMGB1, TLR4, NF-κB, and downstream inflammatory factors in kidney samples was analyzed by quantitative polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. The ratios of TLR4+CXCR4+ PC subsets in the blood and kidneys of mice were determined by flow cytometry. RESULTS: In MRL/lpr mice, Nrf2 was downregulated while HMGB1/TLR4/NF-κB pathway proteins were upregulated. Nrf2 overexpression decreased the expression of HMGB1, TLR4, NF-κB, and its downstream inflammatory cytokines (IL-1ß and TNFα). These cytokines were negatively correlated with an increase in Nrf2 content. PC and TLR4 + CXCR4 + PCs in the blood and kidney samples were significantly increased in MRL/lpr mice; however, they were decreased upon Nrf2 overexpression. CONCLUSION: This study showed severe kidney injury in an LN mouse model and an increased ratio of TLR4 + CXCR4 + PCs. Furthermore, we observed that Nrf2 regulates LN immune response through the Nrf2/HMGB1/TLR4/NF-κB pathway, which can be considered an important target for LN treatment. The clinical value of the findings of our study requires further investigation.

Successful treatment of near-fatal pulmonary embolism and cardiac arrest in an adult patient with fulminant psittacosis-induced severe acute respiratory distress syndrome after veno-venous extracorporeal membrane oxygenation rescue: A case report and follow-up.

Background: Veno-venous extracorporeal membrane oxygenation (ECMO) was successfully performed for the rescue of an adult patient with severe acute respiratory distress syndrome (ARDS) induced by fulminant psittacosis, and then a near-fatal pulmonary embolism (PE) and cardiac arrest (CA) of the same patient was cured through catheter-directed thrombolysis. Case presentation: A 51-year-old female patient was admitted to the hospital on September 10, 2021 due to slurred speech, weakness in lower limbs, dizziness, and nausea. Subsequently, she developed confusion and was transferred to the intensive care unit (ICU), where she received anti-shock, antibiotics, invasive mechanical ventilation (IMV), and veno-venous ECMO due to the diagnosis of severe pneumonia, severe ARDS, and septic shock based on comprehensive physical examination, laboratory tests, and imaging findings. The metagenomic next-gengeration sequencing (m-NGS) in the bronchoalveolar lavage fluid (BALF) suggested that the pathogen was chlamydia psittaci, so the antibiotics were adjusted to doxycycline combined with azithromycin. After withdrawal from ECMO, ultrasound (US) re-examination of the left lower limb revealed inter-muscular vein thrombosis, following which heparin was replaced by subcutaneous injection of 0.4ml enoxaparin sodium twice daily for anti-coagulation therapy. After withdrawal from IMV, the patient suffered sudden CA and successful cardiopulmonary resuscitation (CPR), and emergency pulmonary angiography (PA) was performed to show bilateral main pulmonary artery embolism. After immediate catheter-directed thrombolysis and placement of an inferior vena cava filter, the patient's condition gradually stabilized. Conclusions: Veno-venous ECMO can be successfully performed as an emergency life-saving treatment for patients with severe ARDS induced by fulminant psittacosis, and during ECMO regular examinations should be conducted to detect and manage thrombosis in time, thereby avoiding the occurrence of near-fatal PE and CA.