Fever Promotes T Lymphocyte Trafficking via a Thermal Sensory Pathway Involving Heat Shock Protein 90 and α4 Integrins.

Fever is an evolutionarily conserved response that confers survival benefits during infection. However, the underlying mechanism remains obscure. Here, we report that fever promoted T lymphocyte trafficking through heat shock protein 90 (Hsp90)-induced α4 integrin activation and signaling in T cells. By inducing selective binding of Hsp90 to α4 integrins, but not ß2 integrins, fever increased α4-integrin-mediated T cell adhesion and transmigration. Mechanistically, Hsp90 bound to the α4 tail and activated α4 integrins via inside-out signaling. Moreover, the N and C termini of one Hsp90 molecule simultaneously bound to two α4 tails, leading to dimerization and clustering of α4 integrins on the cell membrane and subsequent activation of the FAK-RhoA pathway. Abolishment of Hsp90-α4 interaction inhibited fever-induced T cell trafficking to draining lymph nodes and impaired the clearance of bacterial infection. Our findings identify the Hsp90-α4-integrin axis as a thermal sensory pathway that promotes T lymphocyte trafficking and enhances immune surveillance during infection.

iCRISEE: an integrative analysis of CRISPR screen by reducing false positive hits.

Clustered regularly interspaced short palindromic repeats associated protein 9 (CRISPR/Cas9) technology has become a popular tool for the study of genome function, and the use of this technology can achieve large-scale screening studies of specific phenotypes. Several analysis tools for CRISPR/Cas9 screening data have been developed, while high false positive rate remains a great challenge. To this end, we developed iCRISEE, an integrative analysis of CRISPR ScrEEn by reducing false positive hits. iCRISEE can dramatically reduce false positive hits and it is robust to different single guide RNA (sgRNA) library by introducing precise data filter and normalization, model selection and valid sgRNA number correction in data preprocessing, sgRNA ranking and gene ranking. Furthermore, a powerful web server has been presented to automatically complete the whole CRISPR/Cas9 screening analysis, where we integrated the main hypothesis in multiple algorithms as a full workflow, including quality control, sgRNA extracting, sgRNA alignment, sgRNA ranking, gene ranking and pathway enrichment. In addition, output of iCRISEE, including result mapping, sample clustering, sgRNA ranking and gene ranking, can be easily visualized and downloaded for publication. Taking together, iCRISEE presents to be the state-of-the-art and user-friendly tool for CRISPR screening data analysis. iCRISEE is available at https://www.icrisee.com.

A New Methodology for High Spatiotemporal Resolution Measurements of Air Volatile Organic Compounds: From Sampling to Data Deconvolution.

Monitoring of volatile organic compounds (VOCs) in air is crucial for understanding their atmospheric impacts and advancing their emission reduction plans. This study presents an innovative integrated methodology suitable for achieving semireal-time high spatiotemporal resolution three-dimensional measurements of VOCs from ground to hundreds of meters above ground. The methodology integrates an active AirCore sampler, custom-designed for deployment from unmanned aerial vehicles (UAV), a proton-transfer-reaction mass spectrometry (PTR-MS) for sample analysis, and a data deconvolution algorithm for improved time resolution for measurements of multiple VOCs in air. The application of the deconvolution technique significantly improves the signal strength of data from PTR-MS analysis of AirCore samples and enhances their temporal resolution by 4 to 8 times to 4-11 s. A case study demonstrates that the methodology can achieve sample collection and analysis of VOCs within 45 min, resulting in >120-360 spatially resolved data points for each VOC measured and achieving a horizontal resolution of 20-55 m at a UAV flight speed of 5 m/s and a vertical resolution of 5 m. This methodology presents new possibilities for acquiring 3-dimensional spatial distributions of VOC concentrations, effectively tackling the longstanding challenge of characterizing three-dimensional VOC distributions in the lowest portion of the atmospheric boundary layer.

Quantification of Methane Emissions from Cold Heavy Oil Production with Sand Extraction in Alberta and Saskatchewan, Canada.

Cold heavy oil production with sand (CHOPS) is an extraction process for heavy oil in Canada, with the potential to lead to higher CH4 venting than conventional oil sites, that have not been adequately characterized. In order to quantify CH4 emissions from CHOPS activities, a focused aerial measurement campaign was conducted in the Canadian provinces of Alberta and Saskatchewan in June 2018. Total CH4 emissions from each of 10 clusters of CHOPS wells (containing 22-167 well sites per cluster) were derived using a mass balance computation algorithm that uses in situ wind data measurement on board aircraft. Results show that there is no statistically significant difference in CH4 emissions from CHOPS wells between the two provinces. Cluster-aggregated emission factors (EF) were determined using correspondingly aggregated production volumes. The average CH4 EF was 70.4 ± 36.9 kg/m3 produced oil for the Alberta wells and 55.1 ± 13.7 kg/m3 produced oil for the Saskatchewan wells. Using these EF and heavy oil production volumes reported to provincial regulators, the annual CH4 emissions from CHOPS were estimated to be 121% larger than CHOPS emissions extracted from Canada's National Inventory Report (NIR) for Saskatchewan. The EF were found to be positively correlated with the percentage of nonpiped production volumes in each cluster, indicating higher emissions for nonpiped wells while suggesting an avenue for methane emission reductions. A comparison with recent measurements indicates relatively limited effectiveness of regulations for Saskatchewan compared to those in Alberta. The results of this study indicate the substantial contribution of CHOPS operations to the underreporting observed in the NIR and provide measurement-based EF that can be used to develop improved emissions inventories for this sector and mitigate CH4 emissions from CHOPS operations.

Quantification of Central and Eastern China's atmospheric CH4 enhancement changes and its contributions based on machine learning approach.

Methane is the second largest anthropogenic greenhouse gas, and changes in atmospheric methane concentrations can reflect the dynamic balance between its emissions and sinks. Therefore, the monitoring of CH4 concentration changes and the assessment of underlying driving factors can provide scientific basis for the government's policy making and evaluation. China is the world's largest emitter of anthropogenic methane. However, due to the lack of ground-based observation sites, little work has been done on the spatial-temporal variations for the past decades and influencing factors in China, especially for areas with high anthropogenic emissions as Central and Eastern China. Here to quantify atmospheric CH4 enhancements trends and its driving factors in Central and Eastern China, we combined the most up-to-date TROPOMI satellite-based column CH4 (xCH4) concentration from 2018 to 2022, anthropogenic and natural emissions, and a random forest-based machine learning approach, to simulate atmospheric xCH4 enhancements from 2001 to 2018. The results showed that (1) the random forest model was able to accurately establish the relationship between emission sources and xCH4 enhancement with a correlation coefficient (R²) of 0.89 and a root mean-square error (RMSE) of 11.98 ppb; (2)The xCH4 enhancement only increased from 48.21±2.02 ppb to 49.79±1.87 ppb from the year of 2001 to 2018, with a relative change of 3.27%±0.13%; (3) The simulation results showed that the energy activities and waste treatment were the main contributors to the increase in xCH4 enhancement, contributing 68.00% and 31.21%, respectively, and the decrease of animal ruminants contributed -6.70% of its enhancement trend.

Potential pathways and genes expressed in Chrysanthemum in response to early fusarium oxysporum infection.

BACKGROUND: Chrysanthemum Fusarium wilt is a common fungal disease caused by Fusarium oxysporum, which causes continuous cropping obstacles and huge losses to the chrysanthemum industry. The defense mechanism of chrysanthemum against F. oxysporum remains unclear, especially during the early stages of the disease. Therefore, in the present study, we analyzed chrysanthemum 'Jinba' samples inoculated with F. oxysporum at 0, 3, and 72 h using RNA-seq. RESULTS: The results revealed that 7985 differentially expressed genes (DEGs) were co-expressed at 3 and 72 h after F. oxysporum infection. We analyzed the identified DEGs using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology. The DEGs were primarily enriched in "Plant pathogen interaction", "MAPK signaling pathway", "Starch and sucrose metabolism", and "Biosynthesis of secondary metabolites". Genes related to the synthesis of secondary metabolites were upregulated in chrysanthemum early during the inoculation period. Furthermore, peroxidase, polyphenol oxidase, and phenylalanine ammonia-lyase enzymes were consistently produced to accumulate large amounts of phenolic compounds to resist F. oxysporum infection. Additionally, genes related to the proline metabolic pathway were upregulated, and proline levels accumulated within 72 h, regulating osmotic balance in chrysanthemum. Notably, the soluble sugar content in chrysanthemum decreased early during the inoculation period; we speculate that this is a self-protective mechanism of chrysanthemums for inhibiting fungal reproduction by reducing the sugar content in vivo. In the meantime, we screened for transcription factors that respond to F. oxysporum at an early stage and analyzed the relationship between WRKY and DEGs in the "Plant-pathogen interaction" pathway. We screened a key WRKY as a research target for subsequent experiments. CONCLUSION: This study revealed the relevant physiological responses and gene expression changes in chrysanthemum in response to F. oxysporum infection, and provided a relevant candidate gene pool for subsequent studies on chrysanthemum Fusarium wilt.

The impact of triglyceride-glucose index on ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: Strokes significantly impair quality of life and incur high economic and societal burdens. The triglyceride and glucose (TyG) index is a biochemical marker of insulin resistance (IR) and may have important value in the prediction of strokes, especially ischemic stroke (IS). Our study aims to investigate the relationship between TyG index and IS and ascertain whether TyG index is independently associated with IS adverse outcomes. METHODS: The Cochrane, Embase, Medline, Web of Science, PubMed, and other relevant English databases and related websites were systematically searched for articles on ''TyG index'' and "stroke" published from inception to April 4, 2022. We reviewed the available literature on the TyG index and its relation to predicting IS occurrence in the general population and adverse clinical outcomes. We calculated odds ratios (OR) of TyG index and its predictability of IS occurrence and adverse outcomes. Statistical analyses were performed using the Meta Package in STATA, version 12.0. RESULTS: A total of 18 studies and 592,635 patients were included in our analysis. The pooled effect values of all stroke types showed that higher TyG index was associated with increased the risk of IS in the general population (OR 1.37; 95% CI 1.22-1.54) in a total sample of 554,334 cases with a high level of heterogeneity (P = 0.000, I2 = 74.10%). In addition, compared to IS patients with a lower TyG index, IS patients with a higher TyG index was associated with higher risk of stroke recurrence (OR: 1.50; 95% CI 1.19-1.89) and increased risk of mortality (OR 1.40 95% CI 1.14-1.71). No correlation was found in the effect value combinations of poor functional outcomes (OR 1.12; 95% CI 0.88-1.43) and neurological worsening (OR: 1.76; 95% CI 0.79-3.95) in a total sample of 38,301 cases with a high level of heterogeneity (P = 0.000; I2 = 77.20%). CONCLUSIONS: TyG index has potential value in optimizing risk stratification for IS in the general population. Furthermore, there is a significant association between high TyG index and many adverse outcomes of stroke, especially stroke recurrence and high mortality. Future studies should focus on multi-center and multi-regional designs in order to further explore the relationship between IS and TyG index.

Ocular aberration measurement with and without an aperture stop using a Shack-Hartmann wavefront sensor.

Pupil size is an important parameter since it governs the magnitude of ocular aberrations. The pupil size of a human eye has significant individual differences and varies with light level and accommodation. In order to accurately measure ocular aberrations under different pupil sizes using a Shack-Hartmann wavefront sensor (SHWFS), two types of relationship matrices R (1) and R (2) were proposed, which corresponded to wavefront reconstruction with and without an aperture stop, respectively. The numerical and experimental results indicated that matrix R (2) can significantly improve the accuracy of wavefront restoration when the incident beam size is inconsistent with the wavefront reconstruction aperture. Meanwhile, the impact of the aperture stop on the reconstruction accuracy will become smaller and smaller as the ratio ρ of the outer area to the detection aperture decreases. This study not only can be used for accurately measuring ocular aberrations under different pupil sizes, but also for other variable aperture aberrations measurement in other applications.

Mesoporous silica nanoparticles combined with AKR1C3 siRNA inhibited the growth of castration-resistant prostate cancer by suppressing androgen synthesis in vitro and in vivo.

Intracrine androgen synthesis plays a critical role in the development of castration-resistant prostate cancer (CRPC). Aldo-keto reductase family 1 member C3 (AKR1C3) is a vital enzyme in the intracrine androgen synthesis pathway. In this study, mesoporous silica nanoparticles (MSNs) were employed to deliver small interfering RNA targeting AKR1C3 (siAKR1C3) to downregulate AKR1C3 expression in CPRC cells. The optimal weight ratio of MSNs/siAKR1C3 was determined by a gel retardation assay. Prostate cancer cells such as VCaP cells, which intracrinally express AKR1C3, and LNCaP-AKR1C3 cells stably transfected with AKR1C3 were used to investigate the antitumour effect of MSNs-siAKR1C3. Fluorescence detection and Western blot analyses were applied to confirm the entrance of MSNs-siAKR1C3 into the cells. A SRB (Sulforhodamine B) assay was employed to assess the cell viability, and a radioimmunoassay was used to measure the androgen concentration. Moreover, real-time PCR (RT-PCR), Western blot analysis and ELISA were used to determine the transcription and expression of prostate-specific antigen (PSA), AKR1C3 and androgen receptor (AR). Meanwhile, a reporter gene assay was performed to determine the AR activity. Additionally, a castrated nude mouse xenograft tumour model was produced to verify the inhibitory effect of MSNs-siAKR1C3 in vivo. The results showed that the optimal weight ratio of MSNs/siAKR1C3 was 140:1, and the complex could effectively enter cells, downregulate AKR1C3 expression, reduce the androgen concentration, inhibit AR activation, and inhibit CRPC development both in vitro and in vivo. These results indicate that decreasing intracrine androgen synthesis and inactivating AR signals by MSNs-siAKR1C3 may be a potential effective method for CRPC treatment.

Hayatine inhibits amino acid-induced mTORC1 activation as a novel mTOR-Rag A/C interaction disruptor.

Abnormal activation of the mechanistic target of rapamycin (mTOR) signaling is commonly observed in many cancers and attracts extensive attention as an oncology drug discovery target, which is encouraged by the success of rapamycin and its analogs (rapalogs) in treatment of mTORC1-hyperactive cancers in both pre-clinic models and clinical trials. However, rapamycin and existing rapalogs have typically short-lasting partial responses due to drug resistance, thereby triggering our interest to investigate a potential mTORC1 inhibitor that is mechanistically different from rapamycin. Here, we report that hayatine, a derivative from Cissampelos, can serve as a potential mTORC1 inhibitor selected from a natural compound library. The unique properties owned by hayatine such as downregulation of mTORC1 activities, induction of mTORC1's translocation to lysosomes followed by autophagy, and suppression on cancer cell growth, strongly emphasize its role as a potential mTORC1 inhibitor. Mechanistically, we found that hayatine disrupts the interaction between mTORC1 complex and its lysosomal adaptor RagA/C by binding to the hydrophobic loop of RagC, leading to mTORC1 inhibition that holds great promise to overcome rapamycin resistance. Taken together, our data shed light on an innovative strategy using structural interruption-based mTORC1 inhibitors for cancer treatment.

Astragaloside IV protects against retinal iron overload toxicity through iron regulation and the inhibition of MAPKs and NF-κB activation.

Iron overload toxicity has been implicated in retinal pigment epithelial cell injury in age-related macular degeneration. This study investigates the effects of astragaloside IV (AS-IV), a potential retinal protective agent, on the toxicity process of retinal iron overload in vivo and in vitro. AS-IV partially restored the retinal expression of rhodopsin and retinal pigment epithelium-specific 65 kDa protein, suppressed oxidative stress and inflammatory markers, and alleviated iron deposition and retinal pathological changes in vivo. Also, AS-IV inhibited the phosphorylation of p38 and ERK mitogen-activated protein kinases (MAPKs), as well as the nuclear translocation of nuclear factor-kappa B (NF-κB). Furthermore, AS-IV prevented cell death by decreasing the ratio of Bax/Bcl-2, caspase-3, and cleaved caspase-3 expression in vitro. Although there are no chelation effects between AS-IV and iron, AS-IV can reduce intracellular iron by regulating iron-handling proteins in ARPE-19 cells (Cav1.2, divalent metal transporter-1, transferrin receptor 1, and heavy-chain ferritin). In conclusion, the results show that AS-IV has significant protective effects against retinal iron overload toxicity and suggest that iron regulation and the inhibition of MAPKs and NF-κB activation might be mechanisms underlying the effects of AS-IV.

Ameliorative effects and mechanisms of salvianic acid A on retinal iron overload in vivo and in vitro.

Excessive iron can be accumulated in the retina and lead to retinal iron overload. Salvianic acid A (SAA) has a variety of pharmacologic effects, but there is only a limited understanding of its benefits for retinal iron overload. The aim of this study was to examine the protective effects and latent mechanisms of SAA on retinal iron overload. SAA reduced iron in the serum and retina, attenuated pathophysiological changes, and reduced retinal iron deposition in the retinas of iron-overloaded mice. It also reduced intracellular iron in ARPE-19 cells by regulating iron-handling proteins and chelating with iron. It also significantly inhibited cellular oxidative and inflammatory damage by increasing the nuclear translocation of nuclear erythroid 2-related factor 2 (Nrf2) while decreasing nuclear factor-kappa B (NF-κB), protecting the ARPE-19 cells from apoptosis by suppressing the Bax/Bcl-2 ratio, cytochrome c release, caspase activation, and poly ADP-ribose polymerase cleavage. The ability of SAA to inhibit apoptosis, increase nuclear Nrf2 expression, and decrease nuclear NF-κB expression was further confirmed in the retinas of iron-overloaded mice. This study demonstrates that SAA shows significant protective effects against retinal iron overload; its mechanisms might be associated with iron chelation; regulation of iron-handling proteins; and inhibition of oxidative stress, inflammation and apoptosis.

Cognitive dysfunction in a patient with migraine and APT1A2 mutation: a case report.

BACKGROUND: Hemiplegic migraine (HM) is a rare type of migraine with aura. Some reports have described the clinical manifestations in HM patients with the ATP1A2 mutation. But the impact of the ATP1A2 mutation on cognitive profile in HM patients has not been evaluated in detail. Here we report a patient with cognitive dysfunction in specific area. CASE PRESENTATION: A 15-year-old boy with an aura that included disturbances in consciousness, associated with fever, vomiting, hemiplegia, and aphasia. He was diagnosed with HM with the ATP1A2 mutation before. He had trouble in mathematics and depicting three-dimensional things. CONCLUSIONS: The HM with ATP1A2 patient could develop permanent cognitive dysfunction. Therefore, the cognitive quotient should be carefully and comprehensively evaluated.

Source apportionment of VOCs in a typical medium-sized city in North China Plain and implications on control policy.

Characteristics of atmospheric VOCs (volatile organic compounds) have been extensively studied in megacities in China, however, they are scarcely investigated in medium/small-sized cities in North China Plain (NCP). A comprehensive research on possible sources of VOCs was conducted in a medium-sized city of NCP, from May to September 2019. A total of 143 canister samples of 8 sites in Xuchang city were collected, and 57 VOC species were detected. The average VOC concentrations were 42.6 ± 31.6 µg/m3, with 53.7 ± 31.0 µg/m3 and 32.1 ± 27. 8 µg/m3, in the morning and afternoon, respectively. Alkenes and aromatics contributed 80% of the total ozone formation potential (OFP). Aromatics accounted for more than 95% of secondary organic aerosol potential (SOAP). VOCs were dominated by the local emission with significant transport from the southeast direction. PMF analysis extracted 6 sources, which were combustion (33.1%), LPG usage (19.3%), vehicular exhaust & fuel evaporation (15.8%), solvent usage (15.2%), industrial (9.11%) and biogenic (7.51%), respectively and they contributed 33.4%, 17.6%, 12.9%, 18.6%, 9.28% and 8.22% to the OFP, respectively. Combustion and LPG usage were the dominant VOC sources; and combustion, solvent usage and LPG usage were the main sources of OFP in Xuchang city, which were different to megacities in China with a high contribution from vehicular exhaust, solvent usage and industry, suggesting specific control strategies on VOCs need to be implemented in medium-sized city such as Xuchang city.

CUDC-907, a novel dual PI3K and HDAC inhibitor, in prostate cancer: Antitumour activity and molecular mechanism of action.

Targeting the androgen receptor (AR) signalling pathway remains the main therapeutic option for advanced prostate cancer. However, resistance to AR-targeting inhibitors represents a great challenge, highlighting the need for new therapies. Activation of the PI3K/AKT pathway and increased expression of histone deacetylases (HDACs) are common aberrations in prostate cancer, suggesting that inhibition of such targets may be a viable therapeutic strategy for this patient population. Previous reports demonstrated that combination of PI3K inhibitors (PI3KIs) with histone deacetylase inhibitors (HDACIs) resulted in synergistic antitumour activities against preclinical models of prostate cancer. In this study, we demonstrate that the novel dual PI3K and HDAC inhibitor CUDC-907 has promising antitumour activity against prostate cancer cell lines in vitro and castration-resistant LuCaP 35CR patient-derived xenograft (PDX) mouse model in vivo. CUDC-907-induced apoptosis was partially dependent on Mcl-1, Bcl-xL, Bim and c-Myc. Further, down-regulation of Wee1, CHK1, RRM1 and RRM2 contributed to CUDC-907-induced DNA damage and apoptosis. In the LuCaP 35CR PDX model, treatment with CUDC-907 resulted in significant inhibition of tumour growth. These findings support the clinical development of CUDC-907 for the treatment of prostate cancer.

[Progress in Application of Two-Dimensional Correlation Spectroscopy for Detection of Food Quality].

In recent years, the food safety and quality has always been a serious issue. Therefore, it is urgent to develop a rapid and widely available method to determine the quality of food. Due to high spectral resolution, good spectral selectivity and good ability of spectrogram analysis, the technology of two-dimensional (2D) correlation spectroscopy is an effective method for solving three major problems encountered by the conventional one-dimensional (1D) spectrum: low selectivity of the spectra, difficulty in extracting the information of the spectral feature and difficulty in spectrogram analysis. Therefore, 2D correlation spectroscopy, which is suited to distinguish similar samples hardly distinguished by the conventional 1D spectroscopy, has been successfully applied in many complex biological systems. The developmental process, the experimental way to obtain spectrum, the fundamental mathematical principle and the properties of 2D correlation spectroscopy were introduced in this paper. At the same time, it is pointed out that the origin of weak characteristic bands of substance can be verified in terms of the positive or negative corss peaks in synchronous 2D correlation spectrum combined with the existence or inexistence of corss peaks in asynchronous 2D correlation spectrum. The application of 2D near-infrared, mid-infrared, fluorescence, and raman correlation spectroscopy in the detection of food quality and adulteration, concentrated specifically on diary product, wine, oil, meat, honey, and rice were reviewed. Finally, the limitations and future development prospects were pointed out.

[Discrimination of adulterated milk based on Euclidian distances between two-dimensional infrared correlation spectra].

Based on Euclidian distances between synchronous two-dimensional infrared correlation spectra, in terms of the average Euclidian distances between unknown samples and "extreme samples", and average intra- and inter-Euclidian distances of samples in the calibration set, a new method for the discrimination of adulterated milk was proposed. Sixteen pure milk samples were collected and 16 adulterated milk samples with urea (0.01-0.3 g x L(-1)), and 16 adulterated milk samples with melamine (0.01-0.3 g x L(-1)) samples were prepared, respectively. The IR absorption spectra of all samples were measured at room temperature. The synchronous two-dimensional correlation spectra were generated from concentration-dependent spectral variation of adulterant in milk. The Euclidian distances were calculated between synchronous two-dimensional infrared correlation spectra of all samples. Then, the classification models were built respectively for adulterated milk with urea, and adiulterated milk with melamine. The "extreme samples", average intra- and inter-Euclidian distances were determined. Finally, the unknown samples in prediction set were predicted using constructed models in terms of classification rules of adulterated milk. The classification accuracy rates for pure milk and adulterated milk were 100%. The effectiveness of the proposed method was verified. The results obtained in this study revealed that synchronous two-dimensional infrared correlation spectra in combination with Euclidian distance has a feasible potential to discriminate adulterated milk and pure milk.

Comprehensive analysis of PSME3: from pan-cancer analysis to experimental validation.

PSME3 plays a significant role in tumor progression. However, the prognostic value of PSME3 in pan-cancer and its involvement in tumor immunity remain unclear. We conducted a comprehensive study utilizing extensive RNA sequencing data from the TCGA (The Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression) databases. Our research revealed abnormal expression levels of PSME3 in various cancer types and unveiled a correlation between high PSME3 expression and adverse clinical outcomes, especially in cancers like liver cancer (LIHC) and lung adenocarcinoma (LUAD). Functional enrichment analysis highlighted multiple biological functions of PSME3, including its involvement in protein degradation, immune responses, and stem cell regulation. Moreover, PSME3 showed associations with immune infiltration and immune cells in the tumor microenvironment, indicating its potential role in shaping the cancer immune landscape. The study also unveiled connections between PSME3 and immune checkpoint expression, with experimental validation demonstrating that PSME3 positively regulates CD276. This suggests that PSME3 could be a potential therapeutic target in immunotherapy. Additionally, we predicted sensitive drugs targeting PSME3. Finally, we confirmed in both single-factor Cox and multiple-factor Cox regression analyses that PSME3 is an independent prognostic factor. We also conducted preliminary validations of the impact of PSME3 on cell proliferation and wound healing in liver cancer. In summary, our study reveals the multifaceted role of PSME3 in cancer biology, immune regulation, and clinical outcomes, providing crucial insights for personalized cancer treatment strategies and the development of immunotherapy.

Correction of the Effect of Humic Acids on the Fluorescence Detection of Polycyclic Aromatic Hydrocarbons by Combination Spectroscopy.

Polycyclic aromatic hydrocarbons (PAHs) are widely distributed in soil and water, but fluorescence spectroscopy for PAHs is often interfered with organic matter in the environment. The aim of this paper is to evaluate a correction method using combined spectral technology in an environment where humic acids and PAHs coexist. In the present work, humic acids and benzo[ghi]perylene were analyzed in various concentrations using fluorescence and near-infrared (NIR) spectroscopy from single and mixed samples. The NIR prediction model of humic acids in mixed samples was established based on synergy interval partial least squares, and the standard curve of fluorescence spectra for humic acids was established at 478 nm (characteristic wavelength of benzo[ghi]perylene). The fluorescence intensity of humic acids in the mixed sample was predicted from the content derived from the NIR spectra. The final correction was carried out by their exclusion from the fluorescence of the mixture at the same wavelength. The corrected fluorescence intensity was linearly correlated with the concentration of benzo[ghi]perylene with R2 = 0.8362, while R2 = 0.3538 before correction. These results give a new insight into the calibration modeling of the combined spectral method.

Oligodendrocytes Play a Critical Role in White Matter Damage of Vascular Dementia.

With the deepening of population aging, the treatment of cognitive impairment and dementia is facing increasing challenges. Vascular dementia (VaD) is a cognitive dysfunction caused by brain blood flow damage and one of the most common causes of dementia after Alzheimer's disease. White matter damage in patients with chronic ischemic dementia often occurs before cognitive impairment, and its pathological changes include leukoaraiosis, myelin destruction and oligodendrocyte death. The pathophysiology of vascular dementia is complex, involving a variety of neuronal and vascular lesions. The current proposed mechanisms include calcium overload, oxidative stress, nitrative stress and inflammatory damage, which can lead to hypoxia-ischemia and demyelination. Oligodendrocytes are the only myelinating cells in the central nervous system and closely associated with VaD. In this review article, we intend to further discuss the role of oligodendrocytes in white matter and myelin injury in VaD and the development of anti-myelin injury target drugs.