A global annual fractional tree cover dataset during 2000-2021 generated from realigned MODIS seasonal data.

Fractional tree cover facilitates the depiction of forest density and its changes. However, it remains challenging to estimate tree cover from satellite data, leading to substantial uncertainties in forest cover changes analysis. This paper generated a global annual fractional tree cover dataset from 2000 to 2021 with 250 m resolution (GLOBMAP FTC). MODIS annual observations were realigned at the pixel level to a common phenology and used to extract twelve features that can differentiate between trees and herbaceous vegetation, which greatly reduced feature dimensionality. A massive training data, consisting of 465.88 million sample points from four high-resolution global forest cover products, was collected to train a feedforward neural network model to predict tree cover. Compared with the validation datasets derived from the USGS circa 2010 global land cover reference dataset, the R2 value, MAE, and RMSE were 0.73, 10.55%, and 17.98%, respectively. This dataset can be applied for assessment of forest cover changes, including both abrupt forest loss and gradual forest gain.

Energetics and Redox Kinetics of Pure Ferrocene-Terminated N-Heterocyclic Carbene Self-Assembled Monolayers on Gold.

N-heterocyclic carbene (NHC) self-assembled monolayers (SAMs) on gold have received considerable attention, but little is known about the lateral interactions between neighboring NHC molecules, their stability when subjected to aggressive oxidizing/reducing conditions, and their interactions with solution ions, all of which are essential for their use in a wide range of applications. To address these deficiencies, we present a comprehensive investigation of two different ferrocene (Fc)-terminated NHC SAMs with different chain lengths and linking groups. Pure monolayers of Fc-terminated NHCs display only a single, symmetrical pair of redox peaks, implying the formation of a homogeneous SAM structure with uniformly distributed Fc/Fc+ redox centers. By comparison, pure Fc-alkylthiol SAMs exhibit complex and impractical redox chemistry and require surface dilution in order to achieve reproducible properties. The NHC SAMs examined in this study exhibit very fast Fc redox kinetics and comparable or even superior stability against the application of multiple potential cycles or long-time holding at constant potential compared to alkylthiol SAMs. Furthermore, ion pairing of Fc+ and hydrophobic perchlorate and other hydrophilic anions is observed with Fc-NHC SAMs, highlighting conditions favorable for future applications of these monolayers. This study should therefore shed light on the very promising characteristics of redox-active NHC SAMs as an alternative to traditional Fc-alkylthiol SAMs for multiple practical applications, including in sensors and electrocatalysis.

Electrostatic-Field-Induced Collapse of Nanobubbles in Nanochannels.

The adsorbed nanobubbles inside the nanochannels can cause fluid transport blockages, which will obviously degrade the nanodevice performance and reduce the lifetime. However, due to small-scale effects, the removal of nanobubbles is a huge challenge at the nanoscale. Herein, molecular dynamics simulations are carried out to study the effect of the electrostatic field on underwater nitrogen nanobubbles confined in nanochannels. It is found that the nanobubbles will collapse under an appropriate electrostatic field, thereby unblocking the transport of water in the nanochannels. The formation of ordered water structures induced by electrostatic fields plays an important role in the removal of nanobubbles from the nanochannels. Our findings provide a convenient, controllable, and remote way to address the blockage problem of nanobubbles in nanochannels, which may have potential applications in improving the performance of fuel cells.

A prediction model based on computed tomography characteristics for identifying malignant from benign sub-centimeter solid pulmonary nodules.

Background: Distinguishing benign from malignant sub-centimeter solid pulmonary nodules (SSPNs) continues to be challenging in clinical practice. Earlier diagnosis is crucial for improving patient survival and prognosis. This study aimed to investigate the risk factors of malignant SSPNs and establish and validate a prediction model based on computed tomography (CT) characteristics to assist in their early diagnosis. Methods: A total of 261 consecutive participants with 261 SSPNs were retrospectively recruited between January 2012 and July 2023 from National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (Center 1), including 161 malignant lesions and 100 benign lesions. Patients were randomly assigned to the training set (n=183) and validation set (n=78) according to a 7:3 ratio. Malignant nodules were confirmed by pathology; and benign nodules were confirmed by follow-up or pathology. Clinical data and CT features were collected to estimate the independent predictors of malignancy of SSPN with multivariate logistic analysis. A clinical prediction model was subsequently established by logistic regression. Furthermore, an additional 69 consecutive patients with 69 SSPNs from The Fourth Hospital of Hebei Medical University (Center 2) between January 2022 and December 2022 were retrospectively included as an external cohort to validate the predictive efficacy of the model. The performance of the prediction model was assessed by sensitivity, specificity, and the area under the receiver operating characteristic curve. Results: There were 113 (61.7%), 48 (61.5%) and 28 (40.6%) malignant SSPNs in the training, internal and external validation sets, respectively. Multivariate logistic analysis revealed four independent predictors of malignant SSPNs: tumor-lung interface (P=0.002), spiculation (P=0.04), air bronchogram (P=0.047), and invisible at the mediastinal window (P=0.003). The area under the curve (AUC) for the prediction model in the training set was 0.875 [95% confidence interval (CI): 0.818, 0.933]; and the sensitivity and specificity were 94.7% and 68.6%, respectively. The AUCs in the internal and external validation set were (0.781; 95% CI: 0.664, 0.897) and (0.873; 95% CI: 0.791, 0.955), respectively; the sensitivity and specificity were 66.7% and 83.3% for the internal validation data, and 100.0% and 61.0% for the external validation data, respectively. Conclusions: The prediction model based on CT characteristics could be helpful for distinguishing malignant SSPNs from benign ones.

Stereoconvergent and Enantioselective Synthesis of Z-Homoallylic Alcohols via Nickel-Catalyzed Reductive Coupling of Z/E-1,3-Dienes with Aldehydes.

Stereoconvergent reactions enable the transformation of mixed stereoisomers into well-defined, chiral products─a crucial strategy for handling Z/E-mixed olefins, which are common but challenging substrates in organic synthesis. Herein, we report a stereoconvergent and highly enantioselective method for synthesizing Z-homoallylic alcohols via the nickel-catalyzed reductive coupling of Z/E-mixed 1,3-dienes with aldehydes. This process is enabled by an N-heterocyclic carbene ligand characterized by C2-symmetric backbone chirality and bulky 2,6-diisopropyl N-aryl substituents. Our method achieves excellent stereocontrol over both enantioselectivity and Z-selectivity in a single step, producing chiral Z-homoallylic alcohols that are valuable in natural products and pharmaceuticals.

The positive role of transforming growth factor-ß1 in ischemic stroke.

Ischemic stroke is one of the most disabling and fatal diseases around the world. The damaged brain tissues will undergo excessive autophagy, vascular endothelial cells injury, blood-brain barrier (BBB) impairment and neuroinflammation after ischemic stroke. However, there is no unified viewpoint on the underlying mechanism of brain damage. Transforming growth factor-ß1 (TGF-ß1), as a multi-functional cytokine, plays a crucial role in the intricate pathological processes and helps maintain the physiological homeostasis of brain tissues through various signaling pathways after ischemic stroke. In this review, we summarize the protective role of TGF-ß1 in autophagic flux, BBB, vascular remodeling, neuroinflammation and other aspects after ischemic stroke. Based on the review, we believe that TGF-ß1 could serve as a key target for treating ischemic stroke.

Preliminary investigation of nitric oxide release from upconverted nanoparticles excited at 808 nm near-infrared for brain tumors.

Upconverted UCNPs@mSiO2-NH2 nanoparticles were synthesized via thermal decomposition while employing the energy resonance transfer principle and the excellent near-infrared (NIR) light conversion property of up-conversion. The 808 nm NIR-excited photocontrolled nitric oxide (NO) release platform was successfully developed by electrostatically loading photosensitive NO donor Roussin's black salt (RBS) onto UCNPs@mSiO2-NH2, enabling the temporal, spatial, and dosimetric regulation of NO release for biological applications of NO. The release of NO ranged from 0.015⁓0.099 mM under the conditions of 2.0 W NIR excitation power, 20 min of irradiation time, and UCNPs@mSiO2-NH2&RBS concentration of 0.25⁓1.25 mg/mL. Therefore, this NO release platform has an anti-tumor effect. In vitro experiments showed that under the NIR light, at concentrations of 0.3 mg/mL and 0.8 mg/mL of UCNPs@mSiO2-NH2&RBS, the activity of glioma (U87) and chordoma (U-CH1) cells, as measured by CCK8 assay, was reduced to 50 %. Cell flow cytometry and Western Blot experiments showed that NO released from UCNPs@mSiO2-NH2&RBS under NIR light induced apoptosis in brain tumor cells. In vivo experiments employing glioma and chordoma xenograft mouse models revealed significant inhibition of tumor growth in the NIR and UCNPs@mSiO2-NH2&RBS group, with no observed significant side effects in the mice. Therefore, NO released by UCNPs@mSiO2-NH2&RBS under NIR irradiation can be used as a highly effective and safe strategy for brain tumor therapy.

Feasibility study of ADCs targeting TROP-2, HER2, and CD46 in Ductal Adenocarcinoma and Intraductal Carcinoma of the prostate.

BACKGROUND: Ductal Adenocarcinoma (DAC) and Intraductal Carcinoma of the Prostate (IDC-P) respond poorly to all the currently available conventional therapies. Given their accurate and efficient elimination of cancer cells, Antibody-Drug Conjugates (ADCs) have become one of the most promising anticancer treatments. However, no ADCs have so far been approved for Prostate Cancer (PCa) treatment. This study investigated TROP-2, HER2, and CD46 expression in DAC/IDC-P samples, indirectly analyzing their preliminary feasibility as therapeutic targets for future treatment of the two conditions. PATIENTS AND METHODS: We conducted a retrospective study involving 184 participants (87 DAC/IDC-P patients and 97 Prostatic Acinar Adenocarcinoma (PAC) patients with a Gleason score ≥ 8) without prior treatment between August 2017 and August 2022. Immunohistochemical staining was employed to detect the differential protein expressions of TROP-2, HER2, and CD46 in DAC/IDC-P, PAC, and normal prostate tissues. RESULTS: Compared to pure PAC tissues, TROP-2 expression was significantly higher in DAC/IDC-P and DAC/IDC-P-adjacent PAC tissues (H-score 68.8 vs. 43.8, p < 0.001, and 59.8 vs. 43.8, p = 0.022, respectively). No significant differences in HER2 expression were observed across different cancer tissues. Compared to both DAC/IDC-P-adjacent PAC and pure PAC tissues, CD46 expression was significantly higher in DAC/IDC-P tissues (42.3 vs. 28.6, p = 0.041, and 42.3 vs. 24.3, p = 0.0035, respectively). CONCLUSIONS: Herein, TROP-2 and CD46 expression was higher in DAC/IDC-P tissues than in pure PAC and normal prostate tissues. This finding implies that ADCs targeting the two proteins hold significant promise as potential future treatments for DAC/IDC-P.

Nitrogen input modulates the effects of coastal acidification on nitrification and associated N2O emission.

Acidification of coastal waters, synergistically driven by increasing atmospheric carbon dioxide (CO2) and intensive land-derived nutrient inputs, exerts significant stresses on the biogeochemical cycles of coastal ecosystem. However, the combined effects of anthropogenic nitrogen (N) inputs and aquatic acidification on nitrification, a critical process of N cycling, remains unclear in estuarine and coastal ecosystems. Here, we showed that increased loading of ammonium (NH4+) in estuarine and coastal waters alleviated the inhibitory effect of acidification on nitrification rates but intensified the production of the potent greenhouse gas nitrous oxide (N2O), thus accelerating global climate change. Metatranscriptomes and natural N2O isotopic signatures further suggested that the enhanced emission of N2O may mainly source from hydroxylamine (NH2OH) oxidation rather than from nitrite (NO2-) reduction pathway of nitrifying microbes. This study elucidates how anthropogenic N inputs regulate the effects of coastal acidification on nitrification and associated N2O emissions, thereby enhancing our ability to predict the feedbacks of estuarine and coastal ecosystems to climate change and human perturbations.

Chitosan-based high-performance flexible supercapacitor via "in-situ co-doping/self-regulation-activation" strategy.

The construction of N, P co-doped hierarchically porous carbons (NPHPC) by a facile and green approach is crucial for high-performance energy storage but still an enormous challenge. Herein, an environment-friendly "in-situ co-doping, self-regulation-activation" strategy is presented to one-pot synthesize NPHPC using a phytic acid-induced polyethyleneimine/chitosan gel (PEI-PA-CS) as single precursor. NPHPC displayed a specific surface area of up to 1494 m2 g-1, high specific capacitance of 449 F g-1 at 1 A g-1, outstanding rate capability and cycling durability in a wide temperature range (-20 to 60 °C). NPHPC and PEI-PA-CS electrolyte assembled symmetric quasi-solid-state flexible supercapacitor presents superb energy outputs of 27.06 Wh kg-1 at power density of 225 W kg-1. For capacitive deionization (CDI), NPHPC also exhibit an excellent salt adsorption capacity of 16.54 mg g-1 in 500 mg L-1 NaCl solution at a voltage of 1.4 V, and regeneration performance. This study provides a valuable reference for the rational design and synthesis of novel biomass-derived energy-storage materials by integrating phytic acid induced heteroatom doping and pore engineering.

Four years of climate warming reduced dark carbon fixation in coastal wetlands.

Dark carbon fixation (DCF), conducted mainly by chemoautotrophs, contributes greatly to primary production and the global carbon budget. Understanding the response of DCF process to climate warming in coastal wetlands is of great significance for model optimization and climate change prediction. Here, based on a 4-yr field warming experiment (average annual temperature increase of 1.5°C), DCF rates were observed to be significantly inhibited by warming in coastal wetlands (average annual DCF decline of 21.6%, and estimated annual loss of 0.08-1.5 Tg C yr-1 in global coastal marshes), thus causing a positive climate feedback. Under climate warming, chemoautotrophic microbial abundance and biodiversity, which were jointly affected by environmental changes such as soil organic carbon and water content, were recognized as significant drivers directly affecting DCF rates. Metagenomic analysis further revealed that climate warming may alter the pattern of DCF carbon sequestration pathways in coastal wetlands, increasing the relative importance of the 3-hydroxypropionate/4-hydroxybutyrate cycle, whereas the relative importance of the dominant chemoautotrophic carbon fixation pathways (Calvin-Benson-Bassham cycle and W-L pathway) may decrease due to warming stress. Collectively, our work uncovers the feedback mechanism of microbially mediated DCF to climate warming in coastal wetlands, and emphasizes a decrease in carbon sequestration through DCF activities in this globally important ecosystem under a warming climate.

GSK2334470 attenuates high salt-exacerbated rheumatoid arthritis progression by restoring Th17/Treg homeostasis.

High salt (HS) consumption is a risk factor for multiple autoimmune disorders via disturbing immune homeostasis. Nevertheless, the exact mechanisms by which HS exacerbates rheumatoid arthritis (RA) pathogenesis remain poorly defined. Herein, we found that heightened phosphorylation of PDPK1 and SGK1 upon HS exposure attenuated FoxO1 expression to enhance the glycolytic capacity of CD4 T cells, resulting in strengthened Th17 but compromised Treg program. GSK2334470 (GSK), a dual PDPK1/SGK1 inhibitor, effectively mitigated the HS-induced enhancement in glycolytic capacity and the overproduction of IL-17A. Therefore, administration of GSK markedly alleviated HS-exacerbated RA progression in collagen-induced arthritis (CIA) model. Collectively, our data indicate that HS consumption subverts Th17/Treg homeostasis through the PDPK1-SGK1-FoxO1 signaling, while GSK could be a viable drug against RA progression in clinical settings.

FGL1: a novel biomarker and target for non-small cell lung cancer, promoting tumor progression and metastasis through KDM4A/STAT3 transcription mechanism.

Non-small cell lung cancer (NSCLC) is characterized by a high incidence rate and poor prognosis worldwide. A deeper insight into the pathogenesis of NSCLC and identification of novel therapeutic targets are essential to improve the prognosis of NSCLC. In this study, we revealed that fibrinogen-like protein 1 (FGL1) promotes proliferation, migration, and invasion of NSCLC cells. Mechanistically, we found that Stat3 acts as a transcription factor and can be recruited to the FGL1 promoter, enhancing FGL1 promoter activity. Lysine-specific demethylase 4A (KDM4A) interacts with Stat3 and facilitates the removal of methyl groups from H3K9me3, thereby enhancing Stat3-mediated transcription of FGL1. Furthermore, we observed that Stat3 and KDM4A promote NSCLC cell proliferation, migration, and invasion partly by upregulating FGL1 expression. Additionally, the expression of FGL1 was significantly higher in cancer tissues (n = 90) than in adjacent non-cancerous tissues (n = 90). Furthermore, patients with high FGL1 expression had a shorter overall survival (OS) compared to those with low FGL1 expression. We measured the expression levels of FGL1 on circulating tumor cells (CTCs) in 65 patients and found that patients with a dynamic decrease in FGL1 expression on CTCs exhibited a better therapeutic response. These findings suggest that the dynamic changes in FGL1 expression can serve as a potential biomarker for predicting treatment efficacy in NSCLC. Overall, this study revealed the significant role and regulatory mechanisms of FGL1 in the development of NSCLC, suggesting its potential as a therapeutic target for patients with NSCLC. Future studies should provide more personalized and effective treatment options for patients with NSCLC to improve clinical outcomes.

Morphological Changes of Peri-Coronary Adipose Tissue Together with Elevated NLR in Acute Myocardial Infarction Patients in-Hospital.

Background: Inflammation triggers atherosclerotic plaque rupture, leading to acute myocardial infarction (AMI). Following AMI, peri-coronary adipose tissue (PCAT) undergoes a transition from lipid-rich to hydrophilic characteristics due to vascular inflammation. This study investigates PCAT changes and neutrophil-to-lymphocyte ratio levels during AMI. Patients and Methods: 60 AMI patients undergoing coronary computed tomography angiography and angiography (Jan 2020-Jun 2022) were studied 60 age, gender, BMI-matched stable angina, and 60 non-coronary artery disease patients were included. Siemens VB20.0 measured PCAT-volume and fat attenuation index (FAI). Neutrophil-to-lymphocyte ratio levels were calculated by peripheral blood tests. Results: The PCAT volume and PCAT-FAI gradually increased across the control, stable angina, and AMI groups, with a corresponding gradual rise in NLR. NLR exhibited weak positive correlation with PCAT-FAI (r=0.35) and PCAT-volume (r=0.24). Multivariable logistic regression identified increased PCAT-volume, PCAT-FAI and neutrophil-to-lymphocyte ratio as possible independent AMI risk factors. No significant PCAT-volume difference was observed between infarct-related artery (IRA) and non-IRA for all three coronary arteries. Only PCAT-FAI around IRA-LAD was higher than non-IRA-LAD (-74.84±6.93 HU vs -79.04±8.68 HU). PCAT-FAI around culprit vessels in AMI was higher than corresponding lesion related vessel in SA. PCAT-volume around narrowed non-IRA in AMI was higher than that of corresponding LRV in SA. PCAT-FAI of narrowed non-IRA-LADs and non-IRA-LCXs in AMI were elevated compared to LADs (-78.46±8.56HU vs -83.13±8.34 HU) and LCXs (-73.83±10.63 HU vs -81.38±7.88 HU) of lesion related vessel in stable angina. Conclusion: We found an association between AMI and inflammation in the coronary perivascular adipose tissue and systemic inflammatory response.

The type of COVID-19 vaccination does not affect reproductive function and pregnancy outcomes in infertile couples.

Introduction: Studies on the effect of vaccine type and two other vaccines other than inactivated vaccines approved in China on in vitro fertilization (IVF) pregnancy outcomes are rare. To complement and confirm the existing findings, this research aimed to investigate whether there are adverse effects of different vaccine types in females and males on reproductive function and clinical pregnancy. Methods: This retrospective study enrolled 6,455 fresh embryo transfer cycles at the First Affiliated Hospital of Zhengzhou University between May 1, 2021, and October 31, 2022. The primary outcome is the clinical pregnancy rate (CPR). At the same time, the secondary results are the number of oocytes retrieved, two pronuclei (2PN) rate, blastocyst formation rate, high-quality blastocyst rate, and semen parameters (volume, density, sperm count, forward motility rate, total motility rate, immobility rate, and DNA fragment index (DFI) rate). Results: In the comparison of ovarian stimulation indicators, no statistically significant differences (P > 0.05) were found in Gn days, endometrial thickness, 2PN rate, metaphase 2 (MII) rate, high-quality embryo rate, and blastocyst formation rate. No significant differences (P>0.05) were found in age, body mass index (BMI), education level, and semen parameters (volume, density, sperm count, forward motility rate, total motility rate, immobility rate, and DFI rate) in these four groups. The multivariate regression model showed that neither the types of vaccines nor the vaccination status of both infertile couples significantly affected clinical pregnancy. Discussion: The type of vaccine does not appear to have an unfavorable effect on ovarian stimulation, embryo development, semen parameters, and clinical pregnancy.

CD57 defines a novel cancer stem cell that drive invasion of diffuse pediatric-type high grade gliomas.

BACKGROUND: Diffuse invasion remains a primary cause of treatment failure in pediatric high-grade glioma (pHGG). Identifying cellular driver(s) of pHGG invasion is needed for anti-invasion therapies. METHODS: Ten highly invasive patient-derived orthotopic xenograft (PDOX) models of pHGG were subjected to isolation of matching pairs of invasive (HGGINV) and tumor core (HGGTC) cells. RESULTS: pHGGINV cells were intrinsically more invasive than their matching pHGGTC cells. CSC profiling revealed co-positivity of CD133 and CD57 and identified CD57+CD133- cells as the most abundant CSCs in the invasive front. In addition to discovering a new order of self-renewal capacities, i.e., CD57+CD133- > CD57+CD133+ > CD57-CD133+ > CD57-CD133- cells, we showed that CSC hierarchy was impacted by their spatial locations, and the highest self-renewal capacities were found in CD57+CD133- cells in the HGGINV front (HGGINV/CD57+CD133- cells) mediated by NANOG and SHH over-expression. Direct implantation of CD57+ (CD57+/CD133- and CD57+/CD133+) cells into mouse brains reconstituted diffusely invasion, while depleting CD57+ cells (i.e., CD57-CD133+) abrogated pHGG invasion. CONCLUSION: We revealed significantly increased invasive capacities in HGGINV cells, confirmed CD57 as a novel glioma stem cell marker, identified CD57+CD133- and CD57+CD133+ cells as a new cellular driver of pHGG invasion and suggested a new dual-mode hierarchy of HGG stem cells.

Necessity for higher teicoplanin doses in older adults: a multicenter prospective observational study in China.

BACKGROUND: Many older adult patients receive low-dose teicoplanin with varied regimens, leading to a lack of clarity on its optimal regimens and toxicity profiles in China. This study aimed to clarify these aspects by analyzing teicoplanin treatment concentrations and toxicities. METHODS: We included older adult patients administered teicoplanin at four tertiary hospitals in Beijing from June 2021 to July 2023, targeting a trough concentration (Cmin) ≥ 10 mg/L. Teicoplanin concentrations and toxicities were monitored dynamically. RESULTS: From 204 patients, we obtained 632 teicoplanin concentrations. Most patients (83.3%) received low-dose regimens. Suboptimal concentrations were found in 66.4% of patients within 7 days of treatment and 17.0% after 15 days. Cmin gradually increased with treatment duration and was influenced initially by creatinine and by both body weight and creatinine from days 8 to 14. The target concentration was achieved in 53.1%, 33.9%, 15.6%, and 5.5% of patients at 3, ≤ 7, 8-14, and ≥ 15 days after withdrawal, respectively. Slow elimination was associated with average Cmin and eGFR. Nephrotoxicity, hepatotoxicity, and thrombocytopenia occurred in 12.5%, 4.1%, and 31.5% of patients, respectively, without significant differences between concentrations. CONCLUSIONS: Most older adult patients were underdosed, indicating a need for dose adjustment. Given the varied risk factors for suboptimal concentrations in different treatment stages, a one-size-fits-all regimen was ineffective. We recommend an initial dose of 400 mg at 12-h intervals for the first three days, with subsequent doses from days 4 to 14 adjusted based on creatinine and body weight; after day 14, a maintenance dose of 200 mg daily is advised. TRIAL REGISTRATION: ChiCTR2100046811; 28/05/2021.

Prevention and care for moisture-associated skin damage: A scoping review.

OBJECTIVE: Moisture-associated skin damage (MASD) is an inflammatory skin condition caused by long-term exposure to a moist environment, which can compromise the integrity of the barrier and increase pain. This scoping review aimed to systematically analyze the research status of prevention and care for MASD. METHODS: We conducted a scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. PubMed, MEDLINE, Scopus, Web of Science, CINAHL, and the Cochrane Database of Systematic Reviews were searched for relevant articles until March 2023. RESULTS: Based on eligibility criteria, 34 research studies and review articles were included. The prevalence of MASD varies greatly in different medical environments and patient groups. The high-risk factors included prolonged exposure to excessive water, chemical irritation such as urine or feces, mechanical factors such as friction or improper removal of medical adhesives and local bacterial colonization. Prevention measures mainly include avoiding skin exposure to moisture, skin cleansing, moisturizing and the treatment of secondary bacterial infection. CONCLUSION: A variety of factors have an impact on MASD. Nurses should select suitable tools to screen high-risk patients and take targeted preventive measures according to the related types of skin injury to reduce the incidence of MASD.

Inflammation-Responsive Mesoporous Silica Nanoparticles with Synergistic Anti-inflammatory and Joint Protection Effects for Rheumatoid Arthritis Treatment.

PURPOSE: Joint destruction is a major burden and an unsolved problem in rheumatoid arthritis (RA) patients. We designed an intra-articular mesoporous silica nanosystem (MSN-TP@PDA-GlcN) with anti-inflammatory and joint protection effects. The nanosystem was synthesized by encapsulating triptolide (TP) in mesoporous silica nanoparticles and coating it with pH-sensitive polydopamine (PDA) and glucosamine (GlcN) grafting on the PDA. The nano-drug delivery system with anti-inflammatory and joint protection effects should have good potency against RA. METHODS: A template method was used to synthesize mesoporous silica (MSN). MSN-TP@PDA-GlcN was synthesized via MSN loading with TP, coating with PDA and grafting of GlcN on PDA. The drug release behavior was tested. A cellular inflammatory model and a rat RA model were used to evaluate the effects on RA. In vivo imaging and microdialysis (MD) system were used to analyze the sustained release and pharmacokinetics in RA rats. RESULTS: TMSN-TP@PDA-GlcN was stable, had good biocompatibility, and exhibited sustained release of drugs in acidic environments. It had excellent anti-inflammatory effects in vitro and in vivo. It also effectively repaired joint destruction in vivo without causing any tissue toxicity. In vivo imaging and pharmacokinetics experiments showed that the nanosystem prolonged the residence time, lowered the Cmax value and enhanced the relative bioavailability of TP. CONCLUSIONS: These results demonstrated that MSN-TP@PDA-GlcN sustained the release of drugs in inflammatory joints and produced effective anti-inflammatory and joint protection effects on RA. This study provides a new strategy for the treatment of RA.

PDIA3 orchestrates effector T cell program by serving as a chaperone to facilitate the non-canonical nuclear import of STAT1 and PKM2.

Dysregulated T cell activation underpins the immunopathology of rheumatoid arthritis (RA), yet the machineries that orchestrate T cell effector program remain incompletely understood. Herein, we leveraged bulk and single-cell RNA sequencing data from RA patients and validated protein disulfide isomerase family A member 3 (PDIA3) as a potential therapeutic target. PDIA3 is remarkably upregulated in pathogenic CD4 T cells derived from RA patients and positively correlates with C-reactive protein level and disease activity score 28. Pharmacological inhibition or genetic ablation of PDIA3 alleviates RA-associated articular pathology and autoimmune responses. Mechanistically, T cell receptor signaling triggers intracellular calcium flux to activate NFAT1, a process that is further potentiated by Wnt5a under RA settings. Activated NFAT1 then directly binds to the Pdia3 promoter to enhance the expression of PDIA3, which complexes with STAT1 or PKM2 to facilitate their nuclear import for transcribing T helper 1 (Th1) and Th17 lineage-related genes, respectively. This non-canonical regulatory mechanism likely occurs under pathological conditions, as PDIA3 could only be highly induced following aberrant external stimuli. Together, our data support that targeting PDIA3 is a vital strategy to mitigate autoimmune diseases, such as RA, in clinical settings.