Integrating iron metabolism-related gene signature to evaluate prognosis and immune infiltration in nasopharyngeal carcinoma.

BACKGROUND: Dysregulation of iron metabolism has been shown to have significant implications for cancer development. We aimed to investigate the prognostic and immunological significance of iron metabolism-related genes (IMRGs) in nasopharyngeal carcinoma (NPC). METHODS: Multiple Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets were analyzed to identify key IMRGs associated with prognosis. Additionally, the immunological significance of IMRGs was explored. RESULTS: A novel risk model was established using the LASSO regression algorithm, incorporating three genes (TFRC, SLC39A14, and ATP6V0D1).This model categorized patients into low and high-risk groups, and Kaplan-Meier analysis revealed significantly shorter progression-free survival for the high-risk group (P < 0.0001). The prognostic model's accuracy was additionally confirmed by employing time-dependent Receiver Operating Characteristic (ROC) curves and conducting Decision Curve Analysis (DCA). High-risk patients were found to correlate with advanced clinical stages, specific tumor microenvironment subtypes, and distinct morphologies. ESTIMATE analysis demonstrated a significant inverse relationship between increased immune, stromal, and ESTIMATE scores and lowered risk score. Immune analysis indicated a negative correlation between high-risk score and the abundance of most tumor-infiltrating immune cells, including dendritic cells, CD8+ T cells, CD4+ T cells, and B cells. This correlation extended to immune checkpoint genes such as PDCD1, CTLA4, TIGIT, LAG3, and BTLA. The protein expression patterns of selected genes in clinical NPC samples were validated through immunohistochemistry. CONCLUSION: This study presents a prognostic model utilizing IMRGs in NPC, which could assist in assessing patient prognosis and provide insights into new therapeutic targets for NPC.

Impact of body mass index on assisted reproductive technology outcomes in patients with polycystic ovary syndrome: a meta-analysis.

The effect of obesity on pregnancy outcomes of patients with polycystic ovary syndrome (PCOS) undergoing assisted reproductive technology (ART) remains unclear. As such, a meta-analysis of recent studies was conducted to probe the effect of being overweight or obese on ART pregnancy outcomes in patients with PCOS. PubMed, Embase, MEDLINE, Scopus and Web of Science were searched from inception to 22 July 2023 without language restrictions. The main indicators were: live birth rate, clinical pregnancy rate, spontaneous abortion rate and multiple pregnancy rate. Ten studies were analysed, with a combined sample size of 247,845. Among patients with PCOS undergoing ART who were overweight or obese, the live birth rate, clinical pregnancy rate, implantation rate and number of retrieved oocytes were lower than in normal-weight patients with PCOS, and the spontaneous abortion rate was higher than in normal-weight patients with PCOS. Obese patients with PCOS undergoing ART had a lower multiple pregnancy rate and a lower number of mature oocytes compared with normal-weight patients with PCOS. The data showed that, among patients with PCOS, being overweight or obese has a negative effect on ART pregnancy outcomes. This meta-analysis may inform guidelines for pregnancy with ART, and encourage overweight or obese patients with PCOS to lose weight.

Assessing NGS-based computational methods for predicting transcriptional regulators with query gene sets.

This article provides an in-depth review of computational methods for predicting transcriptional regulators with query gene sets. Identification of transcriptional regulators is of utmost importance in many biological applications, including but not limited to elucidating biological development mechanisms, identifying key disease genes, and predicting therapeutic targets. Various computational methods based on next-generation sequencing (NGS) data have been developed in the past decade, yet no systematic evaluation of NGS-based methods has been offered. We classified these methods into two categories based on shared characteristics, namely library-based and region-based methods. We further conducted benchmark studies to evaluate the accuracy, sensitivity, coverage, and usability of NGS-based methods with molecular experimental datasets. Results show that BART, ChIP-Atlas, and Lisa have relatively better performance. Besides, we point out the limitations of NGS-based methods and explore potential directions for further improvement. Key points: An introduction to available computational methods for predicting functional TRs from a query gene set.A detailed walk-through along with practical concerns and limitations.A systematic benchmark of NGS-based methods in terms of accuracy, sensitivity, coverage, and usability, using 570 TR perturbation-derived gene sets.NGS-based methods outperform motif-based methods. Among NGS methods, those utilizing larger databases and adopting region-centric approaches demonstrate favorable performance. BART, ChIP-Atlas, and Lisa are recommended as these methods have overall better performance in evaluated scenarios.

NBR1-p62-Nrf2 mediates the anti-pulmonary fibrosis effects of protodioscin.

BACKGROUND: Idiopathic pulmonary fibrosis is a persistent disease of the lung interstitium for which there is no efficacious pharmacological therapy. Protodioscin, a steroidal saponin, possesses diverse pharmacological properties; however, its function in pulmonary fibrosis is yet to be established. Hence, in this investigation, it was attempted to figure out the anti-pulmonary fibrosis influences of protodioscin and its pharmacological properties related to oxidative stress. METHODS: A mouse lung fibrosis model was generated using tracheal injections of bleomycin, followed by intraperitoneal injection of different concentrations of protodioscin, and the levels of oxidative stress and fibrosis were detected in the lungs. Multiple fibroblasts were treated with TGF-ß to induce their transition to myofibroblasts. It was attempted to quantify myofibroblast markers' expression levels and reactive oxygen species levels as well as Nrf2 activation after co-incubation of TGF-ß with fibroblasts and different concentrations of protodioscin. The influence of protodioscin on the expression and phosphorylation of p62, which is associated with Nrf2 activation, were detected, and p62 related genes were predicted by STRING database. The effects of Nrf2 inhibitor or silencing of the Nrf2, p62 and NBR1 genes, respectively, on the activation of Nrf2 by protodioscin were examined. The associations between p62, NBR1, and Keap1 in the activation of Nrf2 by protodioscin was demonstrated using a co-IP assay. Nrf2 inhibitor were used when protodioscin was treated in mice with pulmonary fibrosis and lung tissue fibrosis and oxidative stress levels were detected. RESULTS: In vivo, protodioscin decreased the levels of fibrosis markers and oxidative stress markers and activated Nrf2 in mice with pulmonary fibrosis, and these effects were inhibited by Nrf2 inhibitor. In vitro, protodioscin decreased the levels of myofibroblast markers and oxidative stress markers during myofibroblast transition and promoted Nrf2 downstream gene expression, with reversal of these effects after Nrf2, p62 and NBR1 genes were silenced or Nrf2 inhibitors were used, respectively. Protodioscin promoted the binding of NBR1 to p62 and Keap1, thereby reducing Keap1-Nrf2 binding. CONCLUSION: The NBR1-p62-Nrf2 axis is targeted by protodioscin to reduce oxidative stress and inhibit pulmonary fibrosis.

Effects of cadmium and zinc interactions on the physiological biochemistry and enrichment characteristics of Iris pseudacorus.

Compound pollution with cadmium (Cd) and zinc (Zn) is common in nature. The effects of compounded Cd and Zn on the growth and development of Iris pseudacorus in the environment and the plant's potential to remediate heavy metals in the environment remain unclear. In this study, the effects of single and combined Cd and Zn stress on I. pseudacorus growth and the enrichment of heavy metals in I. pseudacorus seedlings were investigated. The results showed that under Cd (160 µM) and Zn (800 µM) stress, plant growth was significantly inhibited and photosynthetic performance was affected. Cd+Zn200 (160 µM + 200 µM) reduced the levels of malondialdehyde, hydrogen peroxide, and non-protein thiols by 31.29%, 53.20%, and 13.29%, respectively, in the aboveground tissues compared with levels in the single Cd treatment. However, Cd+Zn800 (160 µM + 800 µM) had no effect. Cd and Zn800 inhibited the absorption of mineral elements, while Zn200 had little effect on plants. Compared with that for Cd treatment alone, Cd + Zn200 and Cd+Zn800 reduced the Cd content in aboveground tissues by 54.15% and 49.92%, respectively, but had no significant effect on Cd in the root system. Zn significantly reduced the Cd content in subcellular components and limited the content and proportion of Cd extracted using water and ethanol. These results suggest that a low supply of Zn reduces Cd accumulation in aboveground tissues by promoting antioxidant substances and heavy metal chelating agents, thus protecting the photosynthetic systems. The addition of Zn also reduced the mobility and bioavailability of Cd to alleviate its toxicity in I. pseudacorus.

Leveraging microalgae as a sustainable ingredient for meat analogues.

As the world's population and income levels continue to rise, there is a substantial increase in the demand for meat, which poses significant environmental challenges due to large-scale livestock production. This review explores the potential of microalgae as a sustainable protein source for meat analogues. The nutritional composition, functional properties, and environmental advantages of microalgae are analyzed. Additionally, current obstacles to large-scale microalgal food production are addressed, such as strain development, contamination risks, water usage, and downstream processing. The challenges associated with creating meat-like textures and flavors using techniques like extrusion and emulsion formation with microalgae are also examined. Lastly, considerations related to consumer acceptance, marketing, and regulation are summarized. By focusing on improvements in cultivation, structure, sensory attributes, and affordability, microalgae demonstrate promise as a transformative and eco-friendly protein source to enhance the next generation of meat alternatives.

The effect of refined psychological pain nursing combined with IMB nursing on the pain, sleep and quality of life of patients after cervical cancer surgery.

To explore the effect of refined psychological pain nursing combined with information-motivation-behavioral (IMB) care model on the pain, sleep and quality of life of patients after cervical cancer surgery, so as to provide reference and basis for the nursing of patients after cervical cancer surgery. The clinical data of 798 postoperative cervical cancer patients who were nursing in our hospital from January 2018 to December 2022 were included in this retrospective study and divided into the control group (n = 382) and observation group (n = 416) according to the different care methods. The control group used refined psychological pain nursing, and on this basis, the observation group used IMB nursing to observe and compare the differences in pain, sleep and quality of life between the 2 groups. There was no significant difference in pain between the 2 groups before nursing (P > .05). After nursing, the pain of both groups was significantly improved. The scores of NRS, VAS, and PSEQ of the observation group were significantly better than those of the control group (P < .001). After nursing, the quality of life scores such as emotion, cognition, society, and overall health were significantly higher in the observation group than those of the control group, while physical, fatigue, nausea, vomiting, and pain were significantly lower than those of the control group (P < .05). The negative emotion score of the observation group was significantly lower than that of the control group (P < .001). The residual urine volume and urinary tract infection rate of the observation group were significantly lower than those of the control group (P < .05). The bladder function was significantly better than that of the control group (P < .05). The analgesic effect of refined psychological pain nursing combined with IMB nursing on patients after cervical cancer surgery is better than that of refined psychological pain nursing alone, which can promote pain recovery and further improve the quality of life and sleep quality of patients.

Electric-field control of nonvolatile resistance state of perpendicular magnetic tunnel junction via magnetoelectric coupling.

Magnetic tunnel junctions (MTJs) are the core elements of spintronic devices. Now, the mainstream writing operation of MTJs mainly relies on electric current with high energy dissipation, which can be greatly reduced if an electric field is used instead. In this regard, strain-mediated multiferroic heterostructure composed of MTJ and ferroelectrics are promising with the advantages of room temperature and magnetic field-free as already demonstrated by MTJ with in-plane magnetic anisotropy. However, there is no such report on the perpendicular MTJs (p-MTJs), which have been commercialized. Here, we investigate electric-field control of resistance state of MgO-based p-MTJs in multiferroic heterostructures. A remarkable and nonvolatile manipulation of resistance is demonstrated at room temperature without magnetic field assistance. Through various characterizations and micromagnetic simulation, the manipulation mechanism is uncovered. Our work provides an effective avenue for manipulating p-MTJ resistance by electric fields and is notable for high density and ultralow power spintronic devices.

An Innovative Preauricular Free Flap Pedicled with Retrograde Vascular (PFFPRV) for Pediatric Nasal Reconstruction.

SUMMARY: Nasal reconstruction in pediatric patient is very challenging and it requires consideration of later nasal development. Herein, we introduce an innovative preauricular free flap pedicled with retrograde vascular (PFFPRV) for pediatric nasal reconstruction. In this PFFPRV technique, the retrograde superficial temporal vessels were used as the flap pedicle. The lateral alar artery and angular vein were used as vessels of the nasal recipient zone. The flap vessels were anastomosed directly to the recipient area vessels without additional vessel transplantation. Eight pediatric patients with nasal defects underwent this operation. All patients were followed up for more than 2 years. Patients' medical history data were retrospectively analyzed. Preoperative and postoperative facial photos were compared and analyzed. The satisfaction of patient's parents with the aesthetic results was assessed. All patients were successfully operated without intraoperative complications. None of the procedures required additional blood vessel grafts. One patient developed a vascular crisis the next day after the surgery and underwent vascular exploration operation. The free flaps of all patients survived without wound infection or necrosis. The color difference of flap gradually became unobvious. The transplanted flap did not show obvious contracture or retraction, and the nose was symmetrical and developed well. The parents of all patients were satisfied with the surgical results. We think this PFFPRV technique can be a reasonable alternative strategy for reconstruction of pediatric nasal defect, with no adverse effect on nasal development and no need of vascular transplantation. LEVEL OF EVIDENCE: Level IV, therapeutic study.

[Comparison of in vivo pharmacokinetics of twelve constituents in Qihe Fenqing Yin in normal rats and diabetic rats].

This paper aims to study the pharmacokinetic differences of twelve effective constituents(succinic acid, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, protocatechuic aldehyde, caffeic acid, 5-O-ferulogeninic acid, p-coumaric acid, nuciferine, quercetin, oleanolic acid, and ursolic acid) in Qihe Fenqing Yin in normal and diabetic rats. The diabetic rat model was established by a high-fat diet combined with intraperitoneal injection of streptozocin. A UHPLC-QTRAP-MS/MS method was established for the simultaneous determination of 12 constituents in the plasma of normal rats and model rats after a single intragastric administration of Qihe Fenqing Yin. The results show that the established analytical method has a good linear relationship with the 12 components, and the specificity, accuracy, precision, and stability meet the requirements. The computational pharmacokinetic parameters are fitted by DAS 3.2.8 software, and the results show that the half-life time(t_(1/2)) of the other nine components in the model group was longer than that in the normal group except for caffeic acid, 5-O-ferulogeninic acid, and oleanolic acid. The area under curve(AUC_(0-t)) of cryptochlorogenic acid, p-coumaric acid, ursolic acid, and oleanolic acid increases compared with the normal group. Meanwhile, mean residence time(MRT) delays. The "double peaks" of quercetin and nuciferine in the normal group are not observed in the model group, suggesting that the pharmacokinetic parameters of the drugs in the disease state are significantly different.

NLRP3 inflammasome-mediated premature immunosenescence drives diabetic vascular aging dependent on the induction of perivascular adipose tissue dysfunction.

AIMS: The vascular aging process accelerated by type 2 diabetes mellitus (T2DM) is responsible for the elevated risk of associated cardiovascular diseases (CVDs). Metabolic disorder-induced immune senescence has been implicated in multi-organ/tissue damage. Herein, we sought to determine the role of immunosenescence in diabetic vascular aging and to investigate the underlying mechanisms. METHODS AND RESULTS: Aging hallmarks of the immune system appear prior to the vasculature in streptozotocin (STZ)/high-fat diet (HFD)-induced T2DM mice or db/db mice. Transplantation of aged splenocytes or diabetic splenocytes into young mice triggered vascular senescence and injury compared to normal control splenocyte transfer. RNA-seq profile and validation in immune tissues revealed that the Toll-like receptor 4 (TLR4)- Nuclear factor-kappa B (NF-κB) -NLRP3 axis might be the mediator of diabetic premature immunosenescence. The absence of Nlrp3 attenuated immune senescence and vascular aging during T2DM. Importantly, senescent immune cells, particularly T cells, provoked perivascular adipose tissue (PVAT) dysfunction and alternations in its secretome, which in turn impair vascular biology. In addition, senescent immune cells may uniquely affect vasoconstriction via influencing PVAT. Lastly, rapamycin alleviated diabetic immune senescence and vascular aging, which may be partly due to NLRP3 signaling inhibition. CONCLUSION: These results indicated that NLRP3 inflammasome-mediated immunosenescence precedes and drives diabetic vascular aging. The contribution of senescent immune cells to vascular aging is a combined effect of their direct effects and induction of PVAT dysfunction, the latter of which can uniquely affect vasoconstriction. We further demonstrated that infiltration of senescent T cells in PVAT was increased and associated with PVAT secretome alterations. Our findings suggest that blocking the NLRP3 pathway may prevent early immunosenescence and thus mitigate diabetic vascular aging and damage, and targeting senescent T cells or PVAT might also be the potential therapeutic approach.

Crosstalk between metabolism and cell death in tumorigenesis.

It is generally recognized that tumor cells proliferate more rapidly than normal cells. Due to such an abnormally rapid proliferation rate, cancer cells constantly encounter the limits of insufficient oxygen and nutrient supplies. To satisfy their growth needs and resist adverse environmental events, tumor cells modify the metabolic pathways to produce both extra energies and substances required for rapid growth. Realizing the metabolic characters special for tumor cells will be helpful for eliminating them during therapy. Cell death is a hot topic of long-term study and targeting cell death is one of the most effective ways to repress tumor growth. Many studies have successfully demonstrated that metabolism is inextricably linked to cell death of cancer cells. Here we summarize the recently identified metabolic characters that specifically impact on different types of cell deaths and discuss their roles in tumorigenesis.

Anthropogenic effects on soils in the eastern Tibetan Plateau revealed by geochemical elemental characteristics.

The Tibetan Plateau (TP) constitutes a fragile and sensitive ecological environment, which is vulnerable to global climate change and human activities. To investigate the anthropogenic effects on the TP's environmental system is valuable for guiding human responses and adaptations to future environmental changes. In this study, we detailedly analyzed the geochemical elements of four representative soil sections developed on loess from Ganzi, Jinchuan, Aba, and Chuanzhusi in the eastern TP. The chemical elemental profiles distinctly indicated the presence of typical anthropogenic elements (Cu, Zn, Ni, Cr, Pb, Mn, and Fe), underscoring the substantial influence of human activities on TP soil, and showing spatial variance. Our results indicate that anthropogenic impacts were relatively low at Aba and Ganzi, resulting in a deficit of anthropogenic elements at the surface layer. Whereas at Jinchuan and Chuanzhusi, relatively intense anthropogenic impacts have led to the enrichment of anthropogenic elements in the topsoil. We infer that agricultural activities, increased traffic, and expansion of tourism activities were the major factors affecting the anthropogenic elements of TP soils. Our study highlights the impact of human activities on soil geochemical processes in the Tibetan Plateau.

Clinical study of reoperation for acute type A aortic dissection.

Objective: The initial operation for type A aortic dissection has limitations, and there may be a need for reoperation in cases such as giant pseudoaneurysm formation and reduced blood supply to the distal vessels. In this study, we collected case data of patients who underwent cardiac major vascular surgery at our hospital to analyze the effectiveness of reoperation treatment options for type A aortic dissection and to summarize our treatment experience. Method: Between June 2018 and December 2022, 62 patients with type A aortic dissection (TAAD) underwent reoperation after previous surgical treatment. Of these, 49 patients (45 males) underwent endovascular aortic repair (EVAR) with a mean age of (49.69 ± 10.21) years (30-75 years), and 13 patients (11 males) underwent thoracoabdominal aortic replacement (TAAR) with a mean age of (41.00 ± 11.18) years (23-66 years). In this study, we retrospectively analyzed the recorded data of 62 patients. In addition, we summarized and analyzed their Computed Tomographic Angiography (CTA) results and perioperative complications. Outcome: In the EVAR group, 47 patients (95.92%) were successfully implanted with overlapping stents, and 2 patients died in the perioperative period. Postoperative complications included cerebral infarction (4.08%), acute renal insufficiency (30.61%), pulmonary insufficiency and need for ventilator (6.12%), poor wound healing (2.04%), postoperative reoperation (16.33%), and lower limb ischemia (2.04%). In the TAAR group, 12 patients (92.31%) were successfully revascularized and 1 patient died in the perioperative period. Postoperative complications included cerebral infarction (7.69%), acute kidney injury (46.15%), pulmonary insufficiency and need for ventilator (15.38%), poor wound healing (30.77%) and postoperative reoperation (15.38%). Conclusion: According to the results of the study, compared with TAAR, EVAR was less invasive, faster recovery, and offered a better choice for some high-risk and high-age patients with comorbid underlying diseases. However, the rate of revascularization was higher after EVAR than TAAR due to vascular lesions. Compared with the use of ascending aortic replacement + hemi-aortic arch replacement for acute type A aortic dissection in many countries and regions, the use of ascending aortic replacement + aortic arch replacement + elephant trunk stent is more traumatic in China, but facilitates reoperation. For young patients, the choice of treatment should be individualized combining vascular lesions and long-term quality of life.

Preserved mucosa unroofing facilitated closure of a large gastric defect after endoscopic full-thickness resection.

A 58-year-old woman was found to have a submucosal bulging lesion in the anterior wall of the gastric fundus during a screening esophagogastroscopy. Endosonographic evaluation revealed it to be a 3.1×2.5cm, hypoechoic mass originating from muscularis propria (MP). Endoscopic full-thickness resection (EFR) was attempted. After submucosal injection, a four-fifth circumferential mucosal incision was made around the lesion. Submucosal dissection was performed to unroof the overlying mucosa, which was preserved via the remaining one-fifth circumferential mucosal edge. Thus a mucosal flap was created and turned aside to expose the mass. En bloc resection of the lesion resulted in a 3.5*3.0cm full-thickness defect . The mucosal flap was flipped back and the defect was almost fully covered. Therefore, closure of the defect was accomplished by simply clipping the two edges of the initially incised mucosa. The patient was discharged 2 days later without discomfort. Histopathology confirmed a gastrointestinal stromal tumor (GIST), prognostic group 1.

Synthesis Design and Properties of Ca5(BO3)3F: Bi3+/Eu3+: Insight into Luminescence, Temperature, and Pressure Sensing.

Nowadays, the utilization of noncontact temperature and pressure sensing is experiencing growing popularity. In this work, Bi3+, Eu3+-doped Ca5(BO3)3F (CBOF) phosphors were synthesized via an ionic liquid-assisted electrospinning approach. The effect of molecular weight of polyvinylpyrrolidone on the morphology of CBOF was investigated, and a comprehensive analysis of its formation mechanism was presented. The luminescence properties of CBOF: Bi3+, Eu3+ were studied systematically. The temperature-dependent emission of CBOF: Bi3+, Eu3+ phosphor was discussed, and it displayed thermal sensitivity, which can be attributed to the distinct thermal response emission behaviors of Bi3+ and Eu3+. The investigation of the pressure-dependent emission behavior of the CBOF: Bi3+ phosphor revealed an anomalous phenomenon: with the increase of pressure, the emission peak showed a trend of first a blue shift and then a red shift. This anomaly was discussed in detail. The phosphor exhibits visual color change (blue to cyan), remarkable pressure sensitivity (4.76 nm/GPa), and a high upper pressure limit (24.2 GPa), indicating its potential use as an optical pressure sensor. Consequently, this study presents an innovative synthetic approach for fabricating CBOF, presenting a bifunctional material with promising prospects in the fields of temperature and pressure sensing.

ACE2 Rescues Sepsis-Associated Encephalopathy by Reducing Inflammation, Oxidative Stress, and Neuronal Apoptosis via the Nrf2/Sestrin2 Signaling Pathway.

Neuroinflammation and oxidative stress contribute to the progression of sepsis-associated encephalopathy (SAE). Angiotensin-converting enzyme 2 (ACE2) is considered to be a neuroprotective factor due to its anti-inflammatory and antioxidant properties. However, the role of ACE2 on myeloid cells in regulating SAE and the underlying mechanism warrants further exploration. SAE was induced in ACE2 transgenic (TG), knockout (KO), and bone marrow (BM) chimeric mice by cecal ligation and puncture (CLP). The expression levels of apoptosis-, oxidation- and neuroinflammation-associated mediators and morphological changes were monitored by quantitative real-time PCR analyses and histological examinations in the cortex of septic mice. The contents of angiotensin (Ang) II and Ang-(1-7) along with the activity of ACE2 were examined with commercial kits. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and Sestrin2 was detected by immunoblotting analysis. Our results indicated that the expression of cortical ACE2 was significantly reduced in the early phase of CLP-induced sepsis. Moreover, ACE2 overexpression in TG mice conferred neuroprotection against sepsis, as evidenced by alleviated neuronal apoptosis, oxidative stress, and proinflammatory M1-like microglial polarization, accompanied by upregulation of the Ang-(1-7), Nrf2, and Sestrin2 protein levels. Conversely, ACE2 deficiency in KO mice exacerbated SAE. The neuroprotective effects of ACE2 were further confirmed in wild-type mice transplanted with ACE2-TG and KO BM cells. Therefore, our data suggest that myeloid ACE2 exerts a protective role in the pathogenesis of SAE, potentially by activating Ang-(1-7)-Nrf2/sestrin2 signaling pathway, and highlight that upregulating ACE2 expression and activity may represent a promising approach for the treatment of SAE in patients with sepsis.

In-Situ Metabolic Profiling of Different Kinds of Rheum palmatum L. by Laser Desorption-Dielectric Barrier Discharge Ionization Mass Spectrometry Imaging.

With its high resolving power and sensitivity, mass spectrometry is considered the most informative technique for metabolite qualitation and quantification in the plant sciences. However, the spatial location information, which is crucial for the exploration of plant physiological mechanisms, is lost. Mass spectrometry imaging (MSI) is able to visualize the spatial distribution of a large number of metabolites from the complex sample surface in a single experiment. In this paper, a flexible and low-cost laser desorption-dielectric barrier discharge ionization-MSI (LD-DBDI-MSI) platform was constructed by combining an LD system with an in-line DBDI source, a high-precision sample translation stage, and an ambient mass spectrometer. It can be operated at a spatial resolution of 20 µm in an atmospheric environment and requires minimal sample preparation. This study presents images of in-situ metabolic profiling of two kinds of plants from different origins, a wild and a farmed Rheum palmatum L. From the screen of these two root sections, the wild one presented five more endogenous molecules than the farmed one, which provides information about the differences in metabolomics.

Association of Vitamin D Levels with Risk of Cognitive Impairment and Dementia: A Systematic Review and Meta-Analysis of Prospective Studies.

Background: Emerging evidence suggests the potential relationship between vitamin D deficiency and risk of cognitive impairment or dementia. To what extent the excess risk of dementia conferred by vitamin D deficiency is less clear. Objective: We summarized the current evidence from several aspects and further quantified these associations. Methods: We collected relevant prospective cohort studies by searching PubMed, Embase and Cochrane up to July 2023. The pooled relative risks (RR) were evaluated by random-effects models. Dose-response analyses were conducted by the method of two-stage generalized least squares regression. Results: Of 9,267 identified literatures, 23 were eligible for inclusion in the meta-analyses, among which 9 and 4 literatures were included in the dose-response analyses for the risk of dementia and Alzheimer's disease (AD). Vitamin D deficiency exhibited a 1.42 times risk for dementia (95% confidence interval (CI) = 1.21-1.65) and a 1.57-fold excess risk for AD (95% CI = 1.15-2.14). And vitamin D deficiency was associated with 34% elevated risk with cognitive impairment (95% CI = 1.19-1.52). Additionally, vitamin D was non-linearly related to the risk of dementia (pnonlinearity = 0.0000) and AD (pnonlinearity = 0.0042). The approximate 77.5-100 nmol/L 25-hydroxyvitamin D [25(OH)D] was optimal for reducing dementia risk. And the AD risk seemed to be decreased when the 25(OH)D level >40.1 nmol/L. Conclusions: Vitamin D deficiency was a risk factor for dementia, AD, and cognitive impairment. The nonlinear relationships may further provide the optimum dose of 25(OH)D for dementia prevention.

Administration of USP7 inhibitor p22077 alleviates Angiotensin II (Ang II)-induced atrial fibrillation in Mice.

Atrial fibrillation (AF), the most common cardiac arrhythmia, is an important contributor to mortality and morbidity. Ubquitin-specific protease 7 (USP7), one of the most abundant ubiquitin-specific proteases (USP), participated in many cellular events, such as cell proliferation, apoptosis, and tumourigenesis. However, its role in AF remains unknown. Here, the mice were treated with Ang II infusion to induce the AF model. Echocardiography was used to measure the atrial diameter. Electrical stimulation was programmed to measure the induction and duration of AF. The changes in atrial remodeling were measured using routine histologic analysis. Here, a significant increase in USP7 expression was observed in Ang II-stimulated atrial cardiomyocytes and atrial tissues, as well as in atrial tissues from patients with AF. The administration of p22077, the inhibitor of USP7, attenuated Ang II-induced inducibility and duration of AF, atrial dilatation, connexin dysfunction, atrial fibrosis, atrial inflammation, and atrial oxidase stress, and then inhibited the progression of AF. Mechanistically, the administration of p22077 alleviated Ang II-induced activation of TGF-ß/Smad2, NF-κB/NLRP3, NADPH oxidases (NOX2 and NOX4) signals, the up-regulation of CX43, ox-CaMKII, CaMKII, Kir2.1, and down-regulation of SERCA2a. Together, this study, for the first time, suggests that USP7 is a critical driver of AF and revealing USP7 may present a new target for atrial fibrillation therapeutic strategies.