Effect of Alzheimer Disease on Prognosis of Intensive Care Unit (ICU) Patients: A Propensity Score Matching Analysis.

BACKGROUND The growing number of patients with Alzheimer disease worldwide has become a leading public concern. Whether Alzheimer disease has an impact on the outcomes of critically ill patients remains unclear; therefore, we conducted this study to evaluate comorbid Alzheimer disease in patients in the Intensive Care Unit (ICU). MATERIAL AND METHODS Data were extracted from the Medical Information Mart for Intensive Care-III database, version 1.4. Patients were divided into an Alzheimer disease group and a non-Alzheimer disease group. Differences in all-cause mortality, length of hospital stay, mechanical ventilation rate, and mechanical ventilation duration were analyzed. Propensity score matching (PSM) was performed to compensate for differences in baseline characteristics. The differences in prognosis were compared between groups after PSM. Survival analyses in patients were performed and Cox regression analyses were used to predict prognoses. RESULTS We included 33 935 patients, among which 433 patients were comorbid with Alzheimer disease. After PSM, there were no significant differences in 7-day mortality, but there were significant differences in 28-day mortality (P=0.047) and 90-day mortality (P=0.012) between the 2 groups. There was also a significant difference in the 4-year cumulative survival between the 2 groups (P<0.001). In all patients undergoing surgery, multivariate Cox regression analysis showed that Alzheimer disease comorbidity was significantly associated with 90-day mortality and 4-year mortality. CONCLUSIONS Critical ill patients with Alzheimer disease had higher 28-day and 90-day mortality. Especially for patients undergoing surgery, Alzheimer disease is an independent risk factor affecting long-term survival.

Treatments in psoriasis: from standard pharmacotherapy to nanotechnology therapy.

Psoriasis is a genetic chronic disease mediated by the immune system with systemic and cutaneous manifestations that can significantly deteriorate patients' quality of life. Two-three percent of the population worldwide suffer from psoriasis and it imposes a substantial economic burden on patients. The aetiology is mainly related with genes and environmental factors. The pathophysiology of psoriasis is characterized by T cells and dendritic cells, antimicrobial peptides, genetic predispositions, lipoprotein-2, galactosin-3, fractalkine, vaspin, and human neutrophilic peptides, etc. in the progression of psoriasis. For patients with psoriasis, the traditional treatments include corticosteroids, vitamin D3 analogues, calcineurin inhibitors, methotrexate, cyclosporine, acitretin, phototherapy, and biological agents, etc. Nanodermatology is an emerging, multidisciplinary science that is gaining increasing recognition in the treatment of psoriasis. This review provides a summary of the pathophysiology, epidemiology, clinical diagnosis, and classical pharmacotherapy of psoriasis. The review also summarizes different nanotechnology therapies for effective treatment of psoriasis.

Regulation and enhancement of the nonlinear optical properties of reduced graphene oxide through Au nanospheres and Au@CdS core-shells.

Regulating nonlinear optical (NLO) absorption and refraction properties of graphene is significant in nonlinear photonics. In this work, the functionalizing strategy of quantum dots (QDs) was used for the regulation of the NLO properties of reduced graphene oxide (rGO) with Au nanospheres and Au@CdS core-shells. The third-order NLO properties of rGO-Au and rGO-Au@CdS nanocomposites were investigated by Z-scan technique with 38 ps laser pulses at 532 nm wavelength. The saturation absorption (SA) of rGO was weakened when it was combined with Au nanospheres and switched to reverse saturation absorption (RSA) when combined with Au@CdS core-shells as irradiance intensity increased. The strength of RSA was tunable with the size of Au@CdS core-shells. Meanwhile, the nonlinear susceptibility of rGO was weakened with the complex Au but was tunable with the complex Au@CdS and realized two times enhancement. The effect of charge transfer mechanism was proposed to explain the regulated effect.

Norepinephrine, Dopamine, and Vasopressin in Patients with Sepsis and Preexisting or Acute Heart Failure: A Retrospective Cohort Study.

BACKGROUND The aim of this study was to assess the impact of norepinephrine (NE), norepinephrine plus vasopressin (NE+VAS) and dopamine in patients with sepsis and heart failure. MATERIAL AND METHODS Data were extracted from the Medical Information Mart for Intensive Care III database, v1.4. Adults aged >18 years in an Intensive Care Unit (ICU) who had heart failure and took vasopressors were included. The patients were divided into 3 groups: NE, NE+VAS, and dopamine. Differences in survival, treatment time, and organ function among the 3 groups were compared. Propensity score matching (PSM) was used to screen for possible prognostic differences, and regression analysis was used to further analyze and predict prognoses. RESULTS A total of 1864 patients were included. There were significant differences among the 3 groups in 7-, 28-, and 90-day mortality after PSM. The 5-year survival rates among the 3 groups also were significantly different (P<0.001). After Cox regression analysis, NE+VAS was an independent risk factor affecting 5-year survival (P<0.001). After multiple linear regression, dopamine was the factor related to ICU and hospital lengths of stay. CONCLUSIONS Compared with NE or dopamine alone, NE+VAS can reduce survival in patients with sepsis and heart failure who need vasopressors. Compared with the other 2 treatment options, dopamine can shorten ICU and hospital stays for these patients.

Autonomous Motion of Bubble-Powered Carbonaceous Nanoflask Motors.

We report a carbonaceous nanomotor with a characteristic flask-like hollow structure that can autonomously move under the propulsion of oxygen bubbles. The carbonaceous nanoflask (CNF) motor was fabricated by encapsulating platinum nanoparticles (Pt NPs) into the hollow cavity of the CNF. The internally encapsulated Pt NPs act as catalysts to decompose hydrogen peroxide (H2O2) fuel into oxygen bubbles. The generated oxygen bubbles recoil the motion of the CNF motors. Besides, the velocity of CNF motors can be controlled by adjusting the concentration of the H2O2 solution. The motion velocity increases with the increase of H2O2 concentration, up to 109.25 µm s-1 at 10% H2O2. This study provides important implications for understanding the motion behaviors of nanomotors with an internal cavity, and the self-propelled CNF motors as smart carrier systems have potential applications in the future.

Size confinement and origins of two-photon absorption and refraction in CdSe quantum dots.

Tuning a semiconductor nanomaterial with large two-photon absorption cross section in the near-infrared wavelength and investigating the correlation and origins between its size and third-order nonlinear optical properties are very important in possible applications. In this work, CdSe quantum dots (QDs) with various sizes were successfully prepared, and their size-confined third-order nonlinear optical properties were investigated by Z-scan technique with 100 fs laser pulses at 800 nm wavelength. Both the two-photon absorption and nonlinear refraction were enhanced about 8.1 times with size decrease and then weakened to 2 times with further size decrease. QDs with the diameter of 4.9 nm had the largest nonlinear optical susceptibility of 7.8 × 10-12 esu. The effects of photoinduced dipole moment and local electric field were proposed to explain this trend. And the intrinsic dipole moment and defects in CdSe QDs also had an effect on this nonlinear process.

Surface oxygen-containing defects of graphene nanosheets with tunable nonlinear optical absorption and refraction.

Surface oxygen-containing defects of graphene nanosheets (G NSs) are important for the nonlinear optical (NLO) properties in optoelectric devices. G NSs with different surface oxygen-containing defects are successfully tuned by a chemical reduction process, and are characterized by several experimental measurements of morphology and structure and by spectroscopy. Their NLO properties are measured with the Z-scan technique and the NLO transmission method using a 30 picosecond single-pulse laser source at 532 nm wavelength. Their NLO susceptibility is enhanced 11.8 times (from 0.38 × 10-12 esu to 4.5 × 10-12 esu) with the decrease in the density of surface oxygen-containing groups, while it is reduced 7.2 times (2.7 × 10-12 esu) with a further decrease in oxygen. Accordingly, the nonlinear absorption coefficient of graphene is increased from 0.51 cm GW-1 to 5.90 cm GW-1, and then decreased to 3.41 cm GW-1, indicating that the NLO response of graphene NSs should be weakened whether the component of surface oxygen-containing groups is too large or too small. The local field effect arising from surface oxygen-containing groups and isolated sp2 clusters is the dominant mechanism for the NLO improvement, while the connection of small sp2 clusters depresses the optical nonlinearity. An evolution from two-photon absorption to saturable absorption with the decrease of surface oxygen concentration is obtained. The intensity-related NLO absorption and refraction in NSs are also discussed. Tuning the surface oxygen-containing defects of graphene is a useful way to enhance the optical nonlinearity for potential applications in devices.

Apigenin promotes osteogenic differentiation of human mesenchymal stem cells through JNK and p38 MAPK pathways.

Apigenin is a plant-derived flavonoid and has been reported to prevent bone loss in ovariectomized mice, but the role of apigenin on osteogenic differentiation of human mesenchymal stem cells (hMSCs) has not been reported. In the present study, the effect of apigenin on osteogenic differentiation of hMSCs was explored. Our results showed that apigenin treatment significantly increased alkaline phosphatase (ALP) activity and mineralization in hMSCs. RT-PCR revealed that apigenin markedly up-regulated the mRNA expression of osteopontin (OPN) and the transcription factors runt-related transcription factor 2 (Runx2). The expression of Runx2 and osterix (OSX) proteins were also increased in hMSCs differentiating into osteoblasts after treatment with apigenin. Furthermore, we investigated the signaling pathways responsible for osteogenic differentiation of apigenin in hMSCs. We found that apigenin treatment significantly increased the levels of p-JNK, p-p38 in hMSCs and addition of the inhibitors of JNK (SP600125) or p38 MAPK (SB203580) eliminated the stimulating effects of apigenin. In addition, addition of SP600125 or SB203580 also blocked apigenin-induced ALP activity, OPN, Runx2, and OSX expression and meanwhile inhibited bone nodule formation. Taken together, these findings suggest apigenin promotes the osteogenesis of hMSCs through activation of JNK and p38 MAPK signal pathways which leads to Runx2 and OSX expressions to induce the formation of bone nodule.

Effect of norepinephrine, vasopressin, and dopamine for survivals of the elderly with sepsis and pre-existing heart failure.

Our study focused on evaluating the effect of three common vasoactive drugs on the prognosis of elderly patients with sepsis and pre-existing heart failure. The Medical Information Mart for Intensive Care III database, Version 1.4, was used. Our study included critically ill older patients (aged ≥ 65 years) with sepsis and heart failure treated with vasoactive drugs. Patients were divided into norepinephrine group, norepinephrine combined with vasopressin group, and dopamine group. The baseline characteristics, primary outcome, and secondary outcome measures were compared among the three groups. In total, 1357 elderly patients were included (766 in norepinephrine group, 250 in norepinephrine combined with vasopressin group, and 341 in dopamine group). After propensity score matching, statistically significant differences in 28-d and 90-d mortality (P = 0.046, P = 0.031) were observed; meanwhile, there was a significant difference in the incidence of mechanical ventilation, AKI, and malignant arrhythmias. Cox regression analysis revealed that norepinephrine combined with vasopressin decreased 5-year survival statistically(P = 0.001). Multiple linear regression analysis indicated dopamine as an independent risk factor in reducing ICU and hospital length of stay (P = 0.001, P = 0.017). Logistic regression analysis showed dopamine was an independent risk factor for new-onset arrhythmias (P < 0.001), while norepinephrine combined with vasopressin was an independent risk factor for new-onset malignant arrhythmias (P < 0.001). Norepinephrine in combination with vasopressin decreased survival and increased the incidence of malignant arrhythmias in elderly sepsis patients with pre-existing heart failure. Dopamine alone reduces ICU and hospital length of stay but increases the new-onset arrhythmias.

Effect of 460 nm blue light PBM on human MeWo melanoma cells.

Photobiomodulation (PBM) using 460 nm blue light has been shown to have an inhibitory effect on skin cancer cells. In this study, we used a continuous LED light source with a wavelength of 460 nm and designed various combinations of power density (ranging from 6.4 to 25.6 mW) and dose (ranging from 0.96 to 30.72 J/cm2) to conduct treatment experiments on MeWo cells to investigate the effects of blue light on MeWo melanoma cells. We are focusing on cell viability, cytotoxicity, mitochondrial function, oxidative stress, and apoptosis. We found that blue light inhibits these melanoma cells through oxidative stress and DNA damage, and this inhibition intensifies at higher irradiance levels. Although the cells initially attempt to resist the stress induced by the treatment, they eventually undergo apoptosis over time. These findings contribute to understanding melanoma's molecular response to blue light PBM, lay the groundwork for future clinical applications.

A Mendelian randomization study on causal effects of leisure sedentary behavior on the risk of erectile dysfunction.

BACKGROUND: Erectile dysfunction has been associated with leisure sedentary behavior in several epidemiological and observational studies. However, the interpretation of these findings is difficult due to residual confounding or reverse causality. OBJECTIVES: To explore the causal association between leisure sedentary behavior and erectile dysfunction, and to explore the underlying mechanism using Mendelian randomization. MATERIALS AND METHODS: In the present study, publicly available large-scale genome-wide association studies of leisure sedentary behaviors (television watching, computer use, and driving), erectile dysfunction, sex hormones (total testosterone, bioactive testosterone, estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin, and sex hormone binding globulin), biomarkers of endothelial function (C reactive protein, E-selectin, and matrix metalloproteinase 7), and psychiatric symptoms (depression and anxiety) were used to perform two-sample Mendelian randomization analyses. The inverse variance weighting method was the main method used to estimate the association, and sensitivity analyses were also performed. RESULTS: A greater risk of erectile dysfunction was significantly associated with a higher genetic susceptibility to leisure computer usage (odds ratio = 3.57; 95% confidence interval = 1.78-7.16; p < 0.001). No evidence was obtained to suggest that watching television or driving for leisure increased the risk of erectile dysfunction. No association was found between computer use and depression, anxiety, C reactive protein, E-selectin, matrix metalloproteinase 7, or other sex hormones, with the exception of follicle-stimulating hormone levels (odds ratio = 0.29; 95% confidence interval = 0.12-0.69; p = 0.01). No indication of heterogeneity or pleiotropy was identified by sensitivity analysis. DISCUSSION: Extended computer usage for leisure raised the likelihood of developing erectile dysfunction, which may be associated to lower follicle-stimulating hormone levels; however, the role of endothelial dysfunction and psychological disorders in the development of erectile dysfunction should not be underestimated. Moderate physical activity may help to correct the dysfunction. CONCLUSION: The present study offered substantial evidence for a positive causal association between computer use and the risk of erectile dysfunction. However, a definitive causal association needs to be established by further research.

SPCS, a Novel Classifier System Based on Senescence Axis Regulators Reveals Tumor Microenvironment Heterogeneity and Guides Frontline Therapy for Clear Cell Renal Carcinoma.

RATIONALE: The emerging evidence suggested that senescence regulator genes were involved in multi cancers, which may be utilized as new targets for cancers. However, the dysregulation and clinical impact of senescence regulator genes in clear cell renal cell cancer (ccRCC) were still in foggy. METHODS: Using multiomics data from TCGA-KIRC and other datasets, we comprehensively investigated the function of senescence regulator genes in ccRCC. ccRCC patients could be remodeled into 2 significant different groups basing on senescence regulators expression: senescence-pattern cancer subtype1 (SPCS1) and subtype2 (SPCS2). We further explored clinical characteristics, functional analysis, tumor immune microenvironment, immunotherapy response, genomic mutation and drug sensitivity between the 2 subtypes. Besides, senescence-pattern related risk model was established to determine the patient's prognosis of ccRCC. Finally, the overview of MECP2 function was investigated in multi cancers. RESULTS: ccRCC patients could be divided into SPCS1 (normal aging group) and SPCS2 (Aging disorder group). The 2 subtypes showed significant different clinical characteristics and biological process in ccRCC. SPCS2, an aggressive subtype, comprised higher clinical stage and worse prognosis of ccRCC patients. SPCS2 subtype indicated activated oncogenic signaling pathway and metabolic signatures to prompt cancer expansion. SPCS2 subgroup owned immunocompromised status, which induced immune dysfunction and low ICI therapy response. The genome-copy numbers of SPCS2, including arm-gain and arm-loss was significantly more frequent than SPCS1. In addition, the 2 subtypes argue contrasting drug sensitivity profiles in clinical specimens and matched cell lines. Finally, we constructed a prognostic risk model consisted of each subtype's leading biomarkers, which exerted a satisfied performance for ccRCC patients. CONCLUSION: Senescence regulator-related signature could modify functional pathways and tumor immune microenvironment by genome mutation and pathway interaction. Senescence regulator-related molecular subtype strengthen the understanding of ccRCC' characterization and guide clinical treatment. Targeting senescence regulators may be regard as a proper way in ccRCC.

The Effect of Multi-Fields Synergy from Electric/Light/Thermal/Force Technologies on Photovoltaic Performance of Ba0.06 Bi0.47 Na0.47 TiO3 Ferroelectric Ceramics via the Mg/Co Substitution at A/B Sites.

Currently, it is widely reported that the photovoltaic effect in ferroelectric materials can be promoted by the application of a piezoelectric force, an external electric field, and intense light illumination. Here, a semiconducting ferroelectric composition is introduced, (1-x) Ba0.06 Bi0.47 Na0.47 TiO3 -xMgCoO3 (abbreviated as xMgCo, where x = 0.02-0.08), synthesized through Mg/Co ions codoping. This process effectively narrows the optical bandgaps to a spectrum of 1.38-3.06 eV. Notably, the system exhibits a substantial increase in short-circuit photocurrent density (Jsc ), by the synergy of the electric, light, and thermal fields. The Jsc can still be further enhanced by the extra introduction of a force field. Additionally, the Jsc also shows an obvious increase after the high field pre-poling. The generation of a considerable number of oxygen vacancies due to the Co2+ /Co3+ mixed valence state (in a 1:3 ratio) contributes to the reduced optimal bandgap. The integration of Mg2+ ion at the A-site restrains the loss and sustains robust ferroelectricity (Pr  = 24.1 µC cm-2 ), high polarizability under an electric field, and a significant piezoelectric coefficient (d33  = 102 pC N-1 ). This study provides a novel perspective on the physical phenomena arising from the synergy of multiple fields in ferroelectric photovoltaic materials.

Comparison of NB-UVB combination therapy regimens for vitiligo: A systematic review and network meta-analysis.

BACKGROUND: Vitiligo was an autoimmune disease and some guidelines for the management of vitiligo encouraged the use of NB-UVB combination therapies to enhance repigmentation. OBJECTIVES: To compare the effectiveness of current NB-UVB combination regimen at the improvement in repigmentation through a systematic review and network meta-analysis. METHODS: We searched the electronic databases for randomized controlled trials related to NB-UVB combination therapy for vitiligo till October 2022. STATA15.0 software was applied to carrying out data analysis. RESULTS: A total of 28 eligible studies involving 1194 participants were enrolled in the analysis. The NMA results revealed that compared with NB-UVB, carboxytherapy [OR = 32.35, 95% CI (1.79, 586.05)], Er: YAG laser+ topical 5% 5-FU [OR = 10.74, 95% CI (4.05, 28.49)], needling/micro-needling [OR = 3.42, 95% CI (1.18, 9.88)], betamethasone intramuscular injection [OR = 3.08, 95% CI (1.17, 8.13)], topical tacrolimus [OR = 2.54, 95% CI (1.30, 4.94)], and oral Chinese herbal medicine compound [OR = 2.51, 95% CI (1.40, 4.50)] integrated with NB-UVB were more efficacious in excellent to complete repigmentation response rate (≥75%). Besides, NB-UVB+ Er: YAG laser+ topical 5% 5-FU [OR = 0.17, 95% CI (0.04, 0.67)] and NB-UVB+ needling/micro-needling [OR = 0.24, 95% CI (0.06, 0.88)] were less likely evaluated as ineffective repigmentation response (≤25%). CONCLUSIONS: All combination therapies ranked higher than NB-UVB monotherapy in inducing successful repigmentation and avoiding failed treatment in patients with vitiligo. Comprehensive consideration, NB-UVB+ Er: YAG laser+ topical 5% 5-FU and NB-UVB+ needling/microneedling would be the preferred therapeutic approaches.

Thickness-modulated optical nonlinearity of colloidal CdSe-CdS core-shell nanoplatelets: large two-photon absorption and self-focusing effects.

As a one-dimensional quantum confined material, colloidal semiconductor nanoplatelets have been widely studied as potential nonlinear materials due to their strong exciton effect and large two-photon absorption cross-section similar to that of two-dimensional materials. In this work, CdSe-CdS core-shell nanoplatelets were synthesized and third-order nonlinear optical properties related to shell thickness were measured using the Z-scan method. Measurement revealed a monotonic increase in the imaginary part of the third-order nonlinear susceptibility (Imχ(3)) of CdSe-CdS nanoplatelets, ranging from 0.62 × 10-13 esu to 2.43 × 10-13 esu, with the growth of shell thickness. The real part of the third-order nonlinear susceptibility (Reχ(3)) shows a non-monotonic change between 4.28 × 10-13 esu and 1.99 × 10-13 esu. The trends were further elucidated by analyzing the optical properties of the nanoplatelets, such as absorption, photoluminescence, and quantum yield, and understanding the variations in defect distribution, exciton binding energy, and quantum confinement effects. The results indicated that the appropriate passivation of the CdS shell effectively enhanced the luminescent performance and third-order nonlinearity of the nanoplatelets, while the induced defects and weakened quantum confinement effects due to the continued shell growth resulted in the opposite effect.

Construction of the prognostic model in non-metastatic renal cancer patients with venous tumor thrombus.

Background: Venous system invasion is a prominent characteristic of local progression in renal cancer and treatment-naïve renal cancer patients with venous tumor thrombus (VTT) gained short natural course and poor prognosis. This study aimed to investigate the efficacy of the surgery and prognostic factors in non-metastatic renal cancer patients with VTT and to construct a nomogram prognostic model. Methods: Clinical data of 114 non-metastatic renal cancer patients with VTT who underwent surgical treatment from January 2011 to September 2022 were retrospectively analyzed. In order to find independent risk factors of prognosis, survival analysis was performed via univariate and multivariate Cox regression models and Kaplan-Meier method. Nomogram prognostic model was established to calculate patients' risk scores. Receiver operating characteristic curve and decision curve analysis were conducted to evaluate the efficacy of the prognostic model. Results: A total of 114 patients were included in this study and there were 48, 12, 25, 23, and 6 cases of grade 0-IV VTT. No perioperative death occurred. The 3-year probabilities of overall survival (OS) and 5-year probabilities of OS were 67% and 43.8%, respectively. Multivariate Cox regression analysis revealed that kidney tumor diameter, preoperative lactate dehydrogenase (LDH), and preoperative neutrophils were independent risk factors. Nomogram was constructed to predict prognosis in renal cancer patients with VTT based on above indicators and Mayo VTT grading. The area under the ROC curve of 1-, 2-, 3-, and 5-year OS of the patients were 0.82, 0.67, 0.57, and 0.55 respectively. Conclusions: Surgical treatment enables renal cancer patients with VTT to gain a better prognosis. Kidney tumor diameter, preoperative LDH, and preoperative neutrophils were independent risk factors. The nomogram perfects the Mayo grading, and provides a reliable reference for evaluation of prognosis of renal cancer patients with VTT.

Hyperin up-regulates miR-7031-5P to promote osteogenic differentiation of MC3T3-E1 cells.

OBJECTIVE: To investigate the effects of Hyperin (Hyp) on osteogenic differentiation of MC3T3-E1 cells. METHODS: Differentially expressed miRNA was screened by miRNA Microarray. miR-7031-5P overexpression and knockdown MC3T3-E1 cell models were constructed by transfecting miR-7031-5P mimics and inhibitor. Alizarin red staining (ARS) assay was used to observe the formation of mineralized nodules in MC3T3-E1 cells. ALP activity was detected by using ALP detection kit. Western blot assay was used to examine the changes in osteogenic differentiation-related proteins. The relationship between miR-7031-5P and Wnt7a was revealed by dual luciferase report experiments. RESULTS: We found that miR-7031-5P was up-regulated in MC3T3-E1 cells after Hyp treatment. The results indicated that compared with the untreated group, Hyp promoted the formation of mineralized nodules and the alkaline phosphatase (ALP) activity of MC3T3-E1 cells via overexpressing miR-7031-5P. Besides, elevated miR-7031-5P increased OPN, COL1A1, and Runx2 mRNA expression. More importantly, Wnt7a was identified as the downstream target gene of miR-7031-5P promoting osteogenic differentiation of MC3T3-E1 cells. CONCLUSIONS: Hyp up-regulated miR-7031-5P to promote osteogenic differentiation of MC3T3-E1 cells by targeting Wnt7a.

UDP-glucose pyrophosphorylase as a target for regulating carbon flux distribution and antioxidant capacity in Phaeodactylum tricornutum.

UDP-glucose pyrophosphorylase (UGPase) is a key enzyme for polysaccharide synthesis, and its role in plants and bacteria is well established; however, its functions in unicellular microalgae remain ill-defined. Here, we perform bioinformatics, subcellular localization as well as in vitro and in vivo analyses to elucidate the functions of two UGPs (UGP1 and UGP2) in the model microalga Phaeodactylum tricornutum. Despite differences in amino acid sequence, substrate specificity, and subcellular localization between UGP1 and UGP2, both enzymes can efficiently increase the production of chrysolaminarin (Chrl) or lipids by regulating carbon flux distribution without impairing growth and photosynthesis in transgenic strains. Productivity evaluation indicate that UGP1 play a bigger role in regulating Chrl and lipid production than UGP2. In addition, UGP1 enhance antioxidant capacity, whereas UGP2 is involved in sulfoquinovosyldiacylglycerol (SQDG) synthesis in P. tricornutum. Taken together, the present results suggest that ideal microalgal strains can be developed for the industrial production of Chrl or lipids and lay the foundation for the development of methods to improve oxidative stress tolerance in diatoms.

An attempt to simultaneously quantify the polysaccharide, total lipid, protein and pigment in single Cyclotella cryptica cell by Raman spectroscopy.

BACKGROUND: At present, the conventional methods for determining photosynthetic products of microalgae are usually based on a large number of cell mass to reach the measurement baseline, and the result can only reveal the average state at the population level, which is not feasible for large-scale and rapid screening of specific phenotypes from a large number of potential microalgae mutants. In recent years, single-cell Raman spectra (SCRS) has been proved to be able to rapidly and simultaneously quantify the biochemical components of microalgae. However, this method has not been reported to analyze the biochemical components of Cyclotella cryptica (C. cryptica). Thus, SCRS was first attempt to determine these four biochemical components in this diatom. RESULTS: The method based on SCRS was established to simultaneously quantify the contents of polysaccharide, total lipids, protein and Chl-a in C. cryptica, with thirteen Raman bands were found to be the main marker bands for the diatom components. Moreover, Partial Least Square Regression (PLSR) models based on full spectrum can reliably predict these four cellular components, with Pearson correlation coefficient for these components reached 0.949, 0.904, 0.801 and 0.917, respectively. Finally, based on SCRS data of one isogenic sample, the pairwise correlation and dynamic transformation process of these components can be analyzed by Intra-ramanome Correlation Analysis (IRCA), and the results showed silicon starvation could promote the carbon in C. cryptica cells to flow from protein and pigment metabolism to polysaccharide and lipid metabolism. CONCLUSIONS: First, method for the simultaneous quantification of the polysaccharide, total lipid, protein and pigment in single C. cryptica cell are established. Second, the instant interconversion of intracellular components was constructed through IRCA, which is based on data set of one isogenic population and more precision and timeliness. Finally, total results indicated that silicon deficiency could promote the carbon in C. cryptica cells to flow from protein and pigment metabolism to polysaccharide and lipid metabolism.

Copper Death Inducer, FDX1, as a Prognostic Biomarker Reshaping Tumor Immunity in Clear Cell Renal Cell Carcinoma.

BACKGROUND: Progress in the diagnosis and treatment of clear cell renal cell carcinoma (ccRCC) has significantly prolonged patient survival. However, ccRCC displays an extreme heterogenous characteristic and metastatic tendency, which limit the benefit of targeted or immune therapy. Thus, identifying novel biomarkers and therapeutic targets for ccRCC is of great importance. METHOD: Pan cancer datasets, including the expression profile, DNA methylation, copy number variation, and single nucleic variation, were introduced to decode the aberrance of copper death regulators (CDRs). Then, FDX1 was systematically analyzed in ccRCC to evaluate its impact on clinical characteristics, prognosis, biological function, immune infiltration, and therapy response. Finally, in vivo experiments were utilized to decipher FDX1 in ccRCC malignancy and its role in tumor immunity. RESULT: Copper death regulators were identified at the pancancer level, especially in ccRCC. FDX1 played a protective role in ccRCC, and its expression level was significantly decreased in tumor tissues, which might be regulated via CNV events. At the molecular mechanism level, FDX1 positively regulated fatty acid metabolism and oxidative phosphorylation. In addition, FDX1 overexpression restrained ccRCC cell line malignancy and enhanced tumor immunity by increasing the secretion levels of IL2 and TNFγ. CONCLUSIONS: Our research illustrated the role of FDX1 in ccRCC patients' clinical outcomes and its impact on tumor immunity, which could be treated as a promising target for ccRCC patients.