Spatial Proteomic Profiling of Colorectal Cancer Revealed Its Tumor Microenvironment Heterogeneity.

Colorectal cancer is a predominant malignancy with a second mortality worldwide. Despite its prevalence, therapeutic options remain constrained and surgical operation is still the most useful therapy. In this regard, a comprehensive spatially resolved quantitative proteome atlas was constructed to explore the functional proteomic landscape of colorectal cancer. This strategy integrates histopathological analysis, laser capture microdissection, and proteomics. Spatial proteome profiling of 200 tissue section samples facilitated by the fully integrated sample preparation technology SISPROT enabled the identification of more than 4000 proteins on the Orbitrap Exploris 240 from 2 mm2 × 10 µm tissue sections. Compared with normal adjacent tissues, we identified a spectrum of cancer-associated proteins and dysregulated pathways across various regions of colorectal cancer including ascending colon, transverse colon, descending colon, sigmoid colon, and rectum. Additionally, we conducted proteomic analysis on tumoral epithelial cells and paracancerous epithelium from early to advanced stages in hallmark rectum cancer and sigmoid colon cancer. Bioinformatics analysis revealed functional proteins and cell-type signatures associated with different regions of colorectal tumors, suggesting potential clinical implications. Overall, this study provides a comprehensive spatially resolved functional proteome landscape of colorectal cancer, serving as a valuable resource for exploring potential biomarkers and therapeutic targets.

Pan-cancer analysis of the TRAF family genes and their correlation with prognosis, TME, immune and drug sensitivity.

BACKGROUND: Tumor necrosis factor receptor-associated factors family genes play a pivotal role in tumorigenesis and metastasis, functioning as adapters or E3 ubiquitin ligases across various signaling pathways. To date, limited research has explored the association between tumor necrosis factor receptor-associated factors family genes and the clinicopathological characteristics of tumors, immunity, and the tumor microenvironment (TME). This comprehensive study investigates the relationship between tumor necrosis factor receptor-associated factors family and prognosis, TME, immune response, and drug sensitivity in a pan-cancer context. METHODS: Utilizing current public databases, this study examines the expression levels and prognostic significance of tumor necrosis factor receptor-associated factors family genes in a pan-cancer context through bioinformatic analysis. In addition, it investigates the correlation between tumor necrosis factor receptor-associated factors expression and various factors, including the TME, immune subtypes, stemness scores, and drug sensitivity in pan-cancer. RESULTS: Elevated expression levels of tumor necrosis factor receptor-associated factor 2, 3, 4, and 7 were observed across various cancer types. Patients exhibiting high expression of these genes generally faced a worse prognosis. Furthermore, a significant correlation was noted between the expression of tumor necrosis factor receptor-associated factors family genes and multiple dimensions of the TME, immune subtypes, and drug sensitivity.

CT-based radiomics research for discriminating the risk stratification of pheochromocytoma using different machine learning models: a multi-center study.

OBJECTIVES: The purpose of this study was to explore and verify the value of various machine learning models in preoperative risk stratification of pheochromocytoma. METHODS: A total of 155 patients diagnosed with pheochromocytoma through surgical pathology were included in this research (training cohort: n = 105; test cohort: n = 50); the risk stratification scoring system classified a PASS score of < 4 as low risk and a PASS score of ≥ 4 as high risk. From CT images captured during the non-enhanced, arterial, and portal venous phase, radiomic features were extracted. After reducing dimensions and selecting features, Logistic Regression (LR), Extra Trees, and K-Nearest Neighbor (KNN) were utilized to construct the radiomics models. By adopting ROC curve analysis, the optimal radiomics model was selected. Univariate and multivariate logistic regression analyses of clinical radiological features were used to determine the variables and establish a clinical model. The integration of radiomics and clinical features resulted in the creation of a combined model. ROC curve analysis was used to evaluate the performance of the model, while decision curve analysis (DCA) was employed to assess its clinical value. RESULTS: 3591 radiomics features were extracted from the region of interest in unenhanced and dual-phase (arterial and portal venous phase) CT images. 13 radiomics features were deemed to be valuable. The LR model demonstrated the highest prediction efficiency and robustness among the tested radiomics models, with an AUC of 0.877 in the training cohort and 0.857 in the test cohort. Ultimately, the composite of clinical features was utilized to formulate the clinical model. The combined model demonstrated the best discriminative ability (AUC, training cohort: 0.887; test cohort: 0.874). The DCA of the combined model showed the best clinical efficacy. CONCLUSION: The combined model integrating radiomics and clinical features had an outstanding performance in differentiating the risk of pheochromocytoma and could offer a non-intrusive and effective approach for making clinical decisions.

Heterologous Expression of Phycocyanobilin in Escherichia coli and Determination of Its Antioxidant Capacity In Vitro.

Phycocyanobilin (PCB) is a blue pigment with antioxidant, anti-inflammatory, and anticancer properties. It is used in the medical and cosmetic industries. In this study, a high-expression plasmid, pET-30a-PCB, was constructed for expression of PCB in Escherichia coli BL21(DE3). The PCB was analyzed using UV-visible absorption spectrum, MALDI-TOF-MS, and fluorescence spectra. The stability and half-life of PCB in different serum were determined. The yield of PCB was optimized through single-factor and orthogonal experiments. The optimal expression conditions were determined as a lactose concentration of 5 mmol/L, an induction time of 8 h, an induction temperature of 27 °C, and an induction duration of 22 h. PCB yield of 6.5 mg/L was achieved and subsequently purified using nickel-affinity chromatography. The purified PCB was quantified indirectly using Hist-tag ELISA detection, and the concentration was 11.66 µg/L. In the range of 0-33 µg/mL, the total antioxidant capacity and reducing the capacity of PCB were stronger than Vitamin E (Ve), with 1,1-diphenyl-2-picrylhydrazil (DPPH) scavenging reaching up to 87.07%, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) free radical (ABTS) scavenging up to 100%, hydroxyl radicals (·OH) scavenging up to 64.19%, hydrogen peroxide (H2O2) scavenging up to 78.75%, This study provides theoretical evidence for PCB as a potent antioxidant.

METTL3-mediated m6A modification of SOX4 regulates osteoblast proliferation and differentiation via YTHDF3 recognition.

N6-methyladenosine (m6A), the most prevalent internal modification in mRNA, is related to the pathogenesis of osteoporosis (OP). Although methyltransferase Like-3 (METTL3), an m6A transferase, has been shown to mitigate OP progression, the mechanisms of METTL3-mediated m6A modification in osteoblast function remain unclear. Here, fluid shear stress (FSS) induced osteoblast proliferation and differentiation, resulting in elevated levels of METTL3 expression and m6A modification. Through Methylated RNA Immunoprecipitation Sequencing (MeRIP-seq) and Transcriptomic RNA Sequencing (RNA-seq), SRY (Sex Determining Region Y)-box 4 (SOX4) was screened as a target of METTL3, whose m6A-modified coding sequence (CDS) regions exhibited binding affinity towards METTL3. Further functional experiments demonstrated that knockdown of METTL3 and SOX4 hampered osteogenesis, and METTL3 knockdown compromised SOX4 mRNA stability. Via RNA immunoprecipitation (RIP) assays, we further confirmed the direct interaction between METTL3 and SOX4. YTH N6-Methyladenosine RNA Binding Protein 3 (YTHDF3) was identified as the m6A reader responsible for modulating SOX4 mRNA and protein levels by affecting its degradation. Furthermore, in vivo experiments demonstrated that bone loss in an ovariectomized (OVX) mouse model was reversed through the overexpression of SOX4 mediated by adeno-associated virus serotype 2 (AAV2). In conclusion, our research demonstrates that METTL3-mediated m6A modification of SOX4 plays a crucial role in regulating osteoblast proliferation and differentiation through its recognition by YTHDF3. Our research confirms METTL3-m6A-SOX4-YTHDF3 as an essential axis and potential mechanism in OP.

A bibliometric analysis of trends in the application of platelet-rich plasma in cosmetics research between 2001 and 2022.

BACKGROUND: Several studies have been conducted on using platelet-rich plasma (PRP) to treat cosmetic issues. Nonetheless, no bibliometric analyses of publications in this field exist. Bibliometrics is an effective tool for methodically assessing the current state of research on a particular topic. This study examines the literature published in this field since 2000 and depicts the resulting network. METHODS: The Web of Science Core Collection was searched for any publications mentioning the use of PRP in cosmetic or aesthetic therapy published between 2001 and 2022. The author, region, institution, journal, cited journal, and keywords were extracted, and the bibliometric analysis was carried out using CiteSpace and R studio. RESULTS: There were a total of 306 items retrieved. The first publication in this field appeared in 2001, and the number of articles published increased over the next 21 years. Saedi Nazanin is the author with the most publications. The most prolific nations and institutions were the United States and the Fourth Military Medical University, respectively. Similarly, most articles and citations were found in the Journal of Cosmetic Dermatology and Plastic and Reconstructive Surgery. After performing a cluster analysis on the keywords of published publications, we discovered that most of the published literature focused on using PRP in rejuvenation, mechanism, and combination with MSCs. These topics are still at the frontier of future research. CONCLUSION: Since the first study in this field was published in 2001, PRP used in cosmetic clinics has been studied. Although early effects have been observed, numerous challenges remain, including a lack of higher-quality clinical studies and explanations of PRP's mechanism. The bibliometric analysis conducted for the purpose of this article provides a summary of academic hotspots and research frontiers, as well as insights and pointers for future productive research.

Tea polyphenols protect against Flavobacterium columnare-induced gill injury via suppression of oxidative stress, inflammation, and apoptosis in grass carp.

Flavobacterium columnare (F. columnare) is one of the deadliest fish pathogens causing bacterial gill rot disease in various freshwater fish species globally. Tea polyphenols (TPs) are an inexpensive product extracted from tea that have received much attention as a feed additive in aquaculture. The current study was designed to investigate the underlying mechanisms and protective effects of dietary TPs against F. columnare-induced gill injury via suppression of oxidative stress, apoptosis, and inflammation in grass carp. TPs were not supplemented to the diet (control) and were supplemented at 40, 80, 120, 160 or 200 mg/kg diet. The feeding experiment was carried out for 60 days, followed by a 3-Day F. columnare challenge test. The results showed that 120 mg/kg TPs in the diet exerted the following five protective effects in fish gill: (1) control gill-rot disease and improved histopathology, (2) inhibit excessive apoptosis, (3) enhance the activity of antioxidant enzymes and upregulate related gene expression via the Nrf2/Keap1 pathway, (4) increase the activity of immune enzymes, And (5) mediate inflammatory cytokine gene expression via the JAK/STAT3 pathway. Taken together, dietary supplementation with TPs is a compelling approach to protect the gill function of fish against F. columnare.

Polyphenols as potential preventers of osteoporosis: A comprehensive review on antioxidant and anti-inflammatory effects, molecular mechanisms, and signal pathways in bone metabolism.

Osteoporosis (OP) is a skeletal disorder characterized by decreased bone density, alterations in bone microstructure, and increased damage to the bones. As the population ages and life expectancy increases, OP has become a global epidemic, drawing attention from scientists and doctors. Because of polyphenols have favorable antioxidant and anti-allergy effects, which are regarded as potential methods to prevent angiocardipathy and OP. Polyphenols offer a promising approach to preventing and treating OP by affecting bone metabolism, reducing bone resolution, maintaining bone density, and lowering the differentiation level of osteoclasts (OC). There are multiple ways in which polyphenols affect bone metabolism. This article provides an overview of how polyphenols inhibit oxidative stress, exert antibacterial effects, and prevent the occurrence of OP. Furthermore, we will explore the regulatory mechanisms and signaling pathways implicated in this process.

A novel necroptosis signature for predicting survival in lung adenocarcinoma.

BACKGROUND: To explore the necroptosis-related genes (NRGs) signature and its predictive values in lung adenocarcinoma (LUAD). METHODS: The training cohort consisted of tumor samples from The Cancer Genome Atlas, and the validation set comprised data from the Gene Expression Omnibus. Univariate and multivariate Cox regression analyses were applied to identify the prognostic NRG signature as an independent molecular indicator. Correlation analysis was used for the association assessment between the NRG signature and immune checkpoint molecules. RESULTS: NRGs involved in necroptosis and immune NOD-like receptor signaling. The NRG signature based on eight NRGs can divide tumors into high-risk and low-risk groups, which was significantly associated with worse survival. Multivariate Cox regression analysis showed that this NRG signature remained an independent prognostic indicator. Stratification analyses demonstrated that this NRG signature was still effective for predicting survival in each stratum of age, gender, and tumor stage. The ROC curve showed a good predictive ability using the NRG signature in the validation cohort (AUC = 0.81). The NRG signature was related to immune checkpoint molecules PD - 1, PD-L1, and PD-L2. CONCLUSIONS: The NRG signature could be a novel predictor of the prognosis and may become a potential therapeutic target in LUAD.

Production of capsaicinoid nonivamide from plant oil and vanillylamine via whole-cell biotransformation.

Capsaicinoids are mostly derived from chili peppers and have widespread applications in food, feed, and pharmacology. Compared with plant extraction, the use of microbial cell factories for capsaicinoids production is considered as a more efficient approach. Here, the biotransformation of renewable plant oil and vanillylamine into capsaicinoid nonivamide was investigated. Nonivamide biosynthesis using nonanoic acid and vanillylamine as substrates was achieved in Escherichia coli by heterologous expression of genes encoding amide-forming N-acyltransferase and CoA-ligase. Through increasing nonanoic acid tolerance of chassis cell, screening key enzymes involved in nonivamide biosynthesis and optimizing biotransformation conditions, the nonivamide titer reached 0.5 g/L. By further integrating a route for conversion of oleic acid to nonanoic acid, nonivamide biosynthesis was finally achieved using olive oil and vanillylamine as substrates, yielding a titer of approximately 10.7 mg/L. Results from this study provide valuable information for constructing highly efficient cell factories for the production of capsaicinoid compounds.

Degradation of sulfanilamide in aqueous solution by ionizing radiation: Performance and mechanism.

Sulfonamide (SA) is an emerging contaminants and the efficient treatment of SA containing wastewater remains a challenge. Herein, SA degradation by gamma irradiation has been systematacially studied. SA (10 mg/L) could be totally removed with 1.5 kGy irradiation. Quenching experiments demonstrated that •OH and eaq- were the predominant for SA degradation. SA degradation was reduced with initial concentration increasing, and the removal was faster with pH increasing in the range of 3.1-10.8. The coexisting matters affected SA degradation through changing reactive species, and the introduction of SO42- and Cl- enhanced SA degradation, while CO32- had a negative impact on SA degradation, and the degradation was insignificantly affected when adding humic acid. Gamma irradiation could remain effective in real water matrixes. In conjunction with LC-MS analysis and DFT calculation, possible degradation pathways for SA were proposed. Gamma irradiation could reduce the toxicity of SA, while several byproducts with more toxic were also formed. Furthermore, gamma/priodate (PI) process was promising to enhance SA degradation and mineralization. k value increased by 1.85 times, and mineralization rate increased from 19.51% to 79.19% when adding PI. This study suggested that ionizing radiation was efficient to eliminate SA in wastewater.

Activating Inducible T-cell Costimulator Yields Antitumor Activity Alone and in Combination with Anti-PD-1 Checkpoint Blockade.

In recent years, there has been considerable interest in mAb-based induction of costimulatory receptor signaling as an approach to combat cancer. However, promising nonclinical data have yet to translate to a meaningful clinical benefit. Inducible T-cell costimulator (ICOS) is a costimulatory receptor important for immune responses. Using a novel clinical-stage anti-ICOS immunoglobulin G4 mAb (feladilimab), which induces but does not deplete ICOS+ T cells and their rodent analogs, we provide an end-to-end evaluation of the antitumor potential of antibody-mediated ICOS costimulation alone and in combination with programmed cell death protein 1 (PD-1) blockade. We demonstrate, consistently, that ICOS is expressed in a range of cancers, and its induction can stimulate growth of antitumor reactive T cells. Furthermore, feladilimab, alone and with a PD-1 inhibitor, induced antitumor activity in mouse and humanized tumor models. In addition to nonclinical evaluation, we present three patient case studies from a first-time-in-human, phase I, open-label, dose-escalation and dose-expansion clinical trial (INDUCE-1; ClinicalTrials.gov: NCT02723955), evaluating feladilimab alone and in combination with pembrolizumab in patients with advanced solid tumors. Preliminary data showing clinical benefit in patients with cancer treated with feladilimab alone or in combination with pembrolizumab was reported previously; with example cases described here. Additional work is needed to further validate the translation to the clinic, which includes identifying select patient populations that will benefit from this therapeutic approach, and randomized data with survival endpoints to illustrate its potential, similar to that shown with CTLA-4 and PD-1 blocking antibodies. Significance: Stimulation of the T-cell activation marker ICOS with the anti-ICOS agonist mAb feladilimab, alone and in combination with PD-1 inhibition, induces antitumor activity across nonclinical models as well as select patients with advanced solid tumors.

Pan-Immune-Inflammatory Value in Patients with Non-Small-Cell Lung Cancer Undergoing Neoadjuvant Immunochemotherapy.

Background: We aimed to investigate the predictive value of a systematic serum inflammation index, pan-immune-inflammatory value (PIV), in pathological complete response (pCR) of patients treated with neoadjuvant immunotherapy to further promote ideal patients' selection. Methods: The clinicopathological and baseline laboratory information of 128 NSCLC patients receiving neoadjuvant immunochemotherapy between October 2019 and April 2022 were retrospectively reviewed. We performed least absolute shrinkage and selection operator (LASSO) algorithm to screen candidate serum biomarkers for predicting pCR, which further entered the multivariate logistic regression model to determine final biomarkers. Accordingly, a diagnostic model for predicting individual pCR was established. Kaplan-Meier method was utilized to estimate curves of disease-free survival (DFS), and the Log rank test was analyzed to compare DFS differences between patients with and without pCR. Results: Patients with NSCLC heterogeneously responded to neoadjuvant immunotherapy, and those with pCR had a significant longer DFS than patients without pCR. Through LASSO and the multivariate logistic regression model, PIV was identified as a predictor for predicting pCR of patients. Subsequently, a diagnostic model integrating with PIV, differentiated degree and histological type was constructed to predict pCR, which presented a satisfactory predictive power (AUC, 0.736), significant agreement between actual and our nomogram-predicted pathological response. Conclusion: Baseline PIV was an independent predictor of pCR for NSCLC patients receiving neoadjuvant immunochemotherapy. A significantly longer DFS was achieved in patients with pCR rather than those without pCR; thus, the PIV-based diagnostic model might serve as a practical tool to identify ideal patients for neoadjuvant immunotherapeutic guidance.

Clinical phenotype and genetic function analysis of a rare family with hereditary leiomyomatosis and renal cell carcinoma complicated with Birt-Hogg-Dubé syndrome.

To date, over 200 families with hereditary leiomyomatosis and renal cell carcinoma (HLRCC) and over 600 families with Birt-Hogg-Dubé (BHD) syndrome have been reported, with low incidence. Here, we describe a patient with suspected rare HLRCC complicated by BHD syndrome. The proband (II1) had characteristic cutaneous leiomyoma-like protrusions on the neck and back, a left renal mass and multiple right renal, liver and bilateral lung cysts. Three family members (I1, II2, II3) had a history of renal cancer and several of the aforementioned clinical features. Two family members (II1, II3) diagnosed with fumarate hydratase (FH)-deficient papillary RCC via pathological biopsy carried two heterozygous variants: FH (NM_000143.3) missense mutation c.1189G>A (p.Gly397Arg) and FLCN (NM_144997.5) frameshift mutation c.1579_1580insA (p.Arg527Glnfs*75). No family member carrying a single variant had renal tumours. In HEK293T cells transfected with mutant vectors, mRNA and protein expression after FLCN p.Arg527Glnfs*75 and FH p.Gly397Arg mutations were significantly lower than those in wild-type (WT) cells. Cell immunofluorescence showed altered protein localisation and reduced protein expression after FLCN p.Arg527Glnfs*75 mutation. The FH WT was uniformly distributed in the cytoplasm, whereas FH protein expression was reduced after the p.Gly397Arg mutation and scattered sporadically with altered cell localisation. Patients with two variants may have a significantly increased penetrance of RCC.

Genetically Engineered-Cell-Membrane Nanovesicles for Cancer Immunotherapy.

The advent of immunotherapy has marked a new era in cancer treatment, offering significant clinical benefits. Cell membrane as drug delivery materials has played a crucial role in enhancing cancer therapy because of their inherent biocompatibility and negligible immunogenicity. Different cell membranes are prepared into cell membrane nanovesicles (CMNs), but CMNs have limitations such as inefficient targeting ability, low efficacy, and unpredictable side effects. Genetic engineering has deepened the critical role of CMNs in cancer immunotherapy, enabling genetically engineered-CMN (GCMN)-based therapeutics. To date, CMNs that are surface modified by various functional proteins have been developed through genetic engineering. Herein, a brief overview of surface engineering strategies for CMNs and the features of various membrane sources is discussed, followed by a description of GCMN preparation methods. The application of GCMNs in cancer immunotherapy directed at different immune targets is addressed as are the challenges and prospects of GCMNs in clinical translation.

Selective venous sampling in primary hyperparathyroidism caused by ectopic parathyroid gland: a case report and literature review.

BACKGROUND: As an invasive technique, selective venous sampling (SVS) is considered a useful method to identify a lesion's location to increase the success rate of secondary surgery in patients with primary hyperparathyroidism (pHPT) caused by ectopic parathyroid adenomas. CASE PRESENTATION: We present a case of post-surgical persistent hypercalcemia and elevated parathyroid hormone (PTH) levels in a 44-year-old woman with previously undetected parathyroid adenoma. An SVS was then performed for further localization of the adenoma, as other non-invasive methods showed negative results. After SVS, an ectopic adenoma was suspected in the sheath of the left carotid artery, previously considered as a schwannoma, and was pathologically confirmed after the second operation. Postoperatively, the patient's symptoms disappeared and serum levels of PTH and calcium normalized. CONCLUSIONS: SVS can provide precise diagnosis and accurate positioning before re-operation in patients with pHPT.

Research trends on artificial intelligence and endoscopy in digestive diseases: A bibliometric analysis from 1990 to 2022.

BACKGROUND: Recently, artificial intelligence (AI) has been widely used in gastrointestinal endoscopy examinations. AIM: To comprehensively evaluate the application of AI-assisted endoscopy in detecting different digestive diseases using bibliometric analysis. METHODS: Relevant publications from the Web of Science published from 1990 to 2022 were extracted using a combination of the search terms "AI" and "endoscopy". The following information was recorded from the included publications: Title, author, institution, country, endoscopy type, disease type, performance of AI, publication, citation, journal and H-index. RESULTS: A total of 446 studies were included. The number of articles reached its peak in 2021, and the annual citation numbers increased after 2006. China, the United States and Japan were dominant countries in this field, accounting for 28.7%, 16.8%, and 15.7% of publications, respectively. The Tada Tomohiro Institute of Gastroenterology and Proctology was the most influential institution. "Cancer" and "polyps" were the hotspots in this field. Colorectal polyps were the most concerning and researched disease, followed by gastric cancer and gastrointestinal bleeding. Conventional endoscopy was the most common type of examination. The accuracy of AI in detecting Barrett's esophagus, colorectal polyps and gastric cancer from 2018 to 2022 is 87.6%, 93.7% and 88.3%, respectively. The detection rates of adenoma and gastrointestinal bleeding from 2018 to 2022 are 31.3% and 96.2%, respectively. CONCLUSION: AI could improve the detection rate of digestive tract diseases and a convolutional neural network-based diagnosis program for endoscopic images shows promising results.

Prevalence of ideal cardiovascular health and its relationship with relative handgrip strength in rural northeast China.

Objectives: We aimed to investigate ideal cardiovascular health (CVH), its relationship with handgrip strength, and its components in rural China. Methods: We conducted a cross-sectional study of 3,203 rural Chinese individuals aged ≥35 years in Liaoning Province, China. Of these, 2,088 participants completed the follow-up survey. Handgrip strength was estimated using a handheld dynamometer and was normalized to body mass. Ideal CVH was assessed using seven health indicators (smoking, body mass index, physical activity, diet, cholesterol, blood pressure, and glucose). Binary logistic regression analyses were performed to assess the correlation between handgrip strength and ideal CVH. Results: Women had a higher rate of ideal cardiovascular health (CVH) than men (15.7% vs. 6.8%, P < 0.001). Higher handgrip strength correlated with a higher proportion of ideal CVH (P for trend <0.001). After adjusting for confounding factors, the odds ratios (95% confidence interval) of ideal CVH across increasing handgrip strength tripartite were 1.00 (reference), 2.368 (1.773, 3.164), and 3.642 (2.605, 5.093) in the cross-sectional study and 1.00 (reference), 2.088 (1.074, 4.060), and 3.804 (1.829, 7.913) in the follow-up study (all P < 0.05). Conclusion: In rural China, the ideal CVH rate was low, and positively correlated with handgrip strength. Grip strength can be a rough predictor of ideal CVH and can be used to provide guidelines for improving CVH in rural China.

Insights into the H2O2-Driven Lytic Polysaccharide Monooxygenase Activity on Efficient Cellulose Degradation in the White Rot Fungus Irpex lacteus.

In contrast to O2, H2O2 as the cosubstrate for lytic polysaccharide monooxygenases (LPMOs) exhibits great advantages in industrial settings for cellulose degradation. However, H2O2-driven LPMO reactions from natural microorganisms have not been fully explored and understood. Herein, secretome analysis unraveled the H2O2-driven LPMO reaction in the efficient lignocellulose-degrading fungus Irpex lacteus, including LPMOs with different oxidative regioselectivities and various H2O2-generating oxidases. Biochemical characterization of H2O2-driven LPMO catalysis showed orders of magnitude improvement in catalytic efficiency compared to that of O2-driven LPMO catalysis for cellulose degradation. Significantly, H2O2 tolerance of LPMO catalysis in I. lacteus was an order of magnitude higher than that in other filamentous fungi. In addition, natural reductants, gallic acid, in particular, presented in lignocellulosic biomass could sufficiently maintain LPMO catalytic reactions. Moreover, the H2O2-driven LPMO catalysis exhibited synergy with canonical endoglucanases for efficient cellulose degradation. Taken together, these findings demonstrate the great application potential of the H2O2-driven LPMO catalysis for upgrading cellulase cocktails to further improve cellulose degradation efficiency.

An Engineered Dermal Substitute with Mesenchymal Stem Cells Enhances Cutaneous Wound Healing.

The treatment of refractory cutaneous wounds remains to be a clinical challenge. There is growing evidence to show that mesenchymal stem cells (MSCs) have great potential in promoting wound healing. However, the therapeutic effects of MSCs are greatly dampened by their poor survival and engraftment in the wounds. To address this limitation, in this study, MSCs were grown into a collagen-glycosaminoglycan (C-GAG) matrix to form a dermis-like tissue sheet, named engineered dermal substitute (EDS). When seeded on C-GAG matrix, MSCs adhered rapidly, migrated into the pores, and proliferated readily. When applied onto excisional wounds in healthy and diabetic mice, the EDS survived well, and accelerated wound closure, compared with C-GAG matrix alone or MSCs in collagen hydrogel. Histological analysis revealed that EDS prolonged the retention of MSCs in the wounds, associated with increased macrophage infiltration and enhanced angiogenesis. RNA-Seq analysis of EDS-treated wounds uncovered the expression of abundant human chemokines and proangiogenic factors and their corresponding murine receptors, suggesting a mechanism of ligand/receptor-mediated signals in wound healing. Thus, our results indicate that EDS prolongs the survival and retention of MSCs in the wounds and enhances wound healing.