Malassezia restricta as an unexpected cause of infectious osteomyelitis diagnosed by metagenomic sequencing: a case report and literature review.

BACKGROUND: Malassezia restricta, a lipophilic and lipodependent yeast belonging to the basidiomycetes group, is an opportunistic fungal pathogen associated with various skin diseases, including seborrheic dermatitis and dandruff. Typically, Malassezia infection in neonates manifests as fungemia or hematogenous dissemination to the bone or lungs. However, vertebral osteomyelitis caused by these fungi is rarely reported owing to non-specific clinical presentations and laboratory/imaging findings. The Pathogen Metagenomics Sequencing (PMseq) technique enables direct high-throughput sequencing of infected specimens, facilitating the rapid and accurate detection of all microorganisms in clinical samples through comprehensive reports. CASE PRESENTATION: A 52-year-old male was admitted to our hospital on July 20, 2022 with a 3-month history of ambulatory difficulties and localized low back pain. Magnetic Resonance Imaging (MRI) examination of the spinal column revealed irregular bone destruction affecting the L2, L3, and L5 vertebral bodies. Additionally, low T1 and high T2 intensity lesions were observed at the intervertebral discs between L3 and L5. The presumptive diagnosis of tuberculous spondylitis was made based on the imaging findings, despite negative results in all mycobacterium tests. However, the patient exhibited no improvement after receiving regular anti-tuberculosis treatment for 3 months. Subsequent MRI revealed an expansive abnormal signal within the vertebral body, leading to progressive bone destruction. The absence of spinal tuberculosis or other infective microorganisms was confirmed through culture from blood and pathological tissue from the L4 vertebral body. Subsequently, PMseq was performed on the specimens, revealing M. restricta as the predominant pathogen with the highest relative abundance value. The pathological examination revealed the presence of fungal mycelium in the L4 vertebral body, with positive findings on periodic Schiff-methenamine and periodic acid-Schiff staining. The anti-tuberculosis treatment was discontinued, and an antifungal combination of fluconazole and voriconazole was administered. All symptoms were resolved after 7 consecutive months of treatment, and the patient was able to ambulate autonomously. Vertebral lesions were reduced on MRI during the 13-month follow-up. CONCLUSIONS: M. restricta is not a commonly recognized pathogen associated with infectious vertebral osteomyelitis. However, PMseq can aid in diagnosis, timely treatment, and decision making for some non-specific infectious diseases.

Human skin long noncoding RNA WAKMAR1 regulates wound healing by enhancing keratinocyte migration.

An increasing number of studies reveal the importance of long noncoding RNAs (lncRNAs) in gene expression control underlying many physiological and pathological processes. However, their role in skin wound healing remains poorly understood. Our study focused on a skin-specific lncRNA, LOC105372576, whose expression was increased during physiological wound healing. In human nonhealing wounds, however, its level was significantly lower compared with normal wounds under reepithelialization. We characterized LOC105372576 as a nuclear-localized, RNAPII-transcribed, and polyadenylated lncRNA. In keratinocytes, its expression was induced by TGF-ß signaling. Knockdown of LOC105372576 and activation of its endogenous transcription, respectively, reduced and increased the motility of keratinocytes and reepithelialization of human ex vivo skin wounds. Therefore, LOC105372576 was termed "wound and keratinocyte migration-associated lncRNA 1" (WAKMAR1). Further study revealed that WAKMAR1 regulated a network of protein-coding genes important for cell migration, most of which were under the control of transcription factor E2F1. Mechanistically, WAKMAR1 enhanced E2F1 expression by interfering with E2F1 promoter methylation through the sequestration of DNA methyltransferases. Collectively, we have identified a lncRNA important for keratinocyte migration, whose deficiency may be involved in the pathogenesis of chronic wounds.

The role of positive nerve root sedimentation sign in the treatment of patients undergoing lumbar disc herniation.

BACKGROUND: To investigate the efficacy of percutaneous transforaminal endoscopic discectomy (PTED) in the treatment of patients who were diagnosed with lumbar disc herniation (LDH) with positive nerve root sedimentation sign (NRSS). METHODS: A total of 86 patients who underwent LDH were recruited and divided into NRSS-positive group (n = 49) and NRSS-negative group (n = 37). The visual analog scale (VAS), Japanese Orthopaedic Association (JOA), and Oswestry disability index (ODI) were used to evaluate the low back pain and functional recovery and were compared between the two groups. RESULTS: There were no significant differences in the demographic parameters between the two groups. The average area of the dural sac compression in the NRSS-positive group was significantly higher than that in the NRSS-negative group. Patients with a positive NRSS showed a better low back pain relief than those with a negative NRSS at 1 week and 1 month after surgery. The JOA and ODI in the NRSS-positive group were better than those in the NRSS-negative group at 3 months and 6 months postoperatively. The apparent efficiency of JOA and the excellent and good rate of ODI in the negative group was lower than that in the positive group at 6 months after surgery. CONCLUSIONS: Patients undergoing LDH with a positive NRSS showed better pain relief and functional recovery than those with a negative NRSS. The present study suggested that NRSS might be a valuable sign and associated with better clinical outcomes in patients undergoing LDH with the treatment of PTED.

The Immune Functions of Keratinocytes in Skin Wound Healing.

As the most dominant cell type in the skin, keratinocytes play critical roles in wound repair not only as structural cells but also exerting important immune functions. This review focuses on the communications between keratinocytes and immune cells in wound healing, which are mediated by various cytokines, chemokines, and extracellular vesicles. Keratinocytes can also directly interact with T cells via antigen presentation. Moreover, keratinocytes produce antimicrobial peptides that can directly kill the invading pathogens and contribute to wound repair in many aspects. We also reviewed the epigenetic mechanisms known to regulate keratinocyte immune functions, including histone modifications, non-protein-coding RNAs (e.g., microRNAs, and long noncoding RNAs), and chromatin dynamics. Lastly, we summarized the current evidence on the dysregulated immune functions of keratinocytes in chronic nonhealing wounds. Based on their crucial immune functions in skin wound healing, we propose that keratinocytes significantly contribute to the pathogenesis of chronic wound inflammation. We hope this review will trigger an interest in investigating the immune roles of keratinocytes in chronic wound pathology, which may open up new avenues for developing innovative wound treatments.

Building a Competing Endogenous RNA Network to Find Potential Long Non-Coding RNA Biomarkers for Pheochromocytoma.

BACKGROUND/AIMS: Accumulating evidence has shown that long non-coding RNAs (lncRNAs) in competing endogenous RNA (ceRNA) networks play crucial roles in tumor survival and patient prognosis; however, studies investigating ceRNA networks in pheochromocytoma (PCC) are lacking. In this study, we investigated the pathogenesis of PCC and whether lncRNAs acting through ceRNAs networks were associated with prognosis. METHODS: A total of 183 PCC samples and 3 control samples from The Cancer Genome Atlas database were analyzed. The Empirical Analysis of Digital Gene Expression Data package in R (edgeR) was used to analyze differentially expressed RNAs. Biological processes and pathways functional enrichment analysis were performed based on the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. LncRNA/mRNA/miRNA ceRNA network was constructed by Cytoscape v3.0 software based on the differentially expressed RNAs Survival package in R was used to perform survival analysis. RESULTS: In total, 554 differentially expressed lncRNAs, 1775 mRNAs and 40 miRNAs were selected for further analysis. Subsequently, 23 lncRNAs, 22 mRNAs, and 6 miRNAs were included in the constructed ceRNA network. Meanwhile, two of the 23 lncRNAs (C9orf147 and BSN-AS2) were identified as independent predictors of overall survival in PCC patients (P< 0.05). CONCLUSION: This study improves the understanding of lncRNA-related ceRNA networks in PCC and suggests that the lncRNAs C9orf147 and BSN-AS2 could be independent prognostic biomarkers and potential therapeutic targets for PCC.

Transition from inflammation to proliferation: a critical step during wound healing.

The ability to rapidly restore the integrity of a broken skin barrier is critical and is the ultimate goal of therapies for hard-to-heal-ulcers. Unfortunately effective treatments to enhance healing and reduce scarring are still lacking. A deeper understanding of the physiology of normal repair and of the pathology of delayed healing is a prerequisite for the development of more effective therapeutic interventions. Transition from the inflammatory to the proliferative phase is a key step during healing and accumulating evidence associates a compromised transition with wound healing disorders. Thus, targeting factors that impact this phase transition may offer a rationale for therapeutic development. This review summarizes mechanisms regulating the inflammation-proliferation transition at cellular and molecular levels. We propose that identification of such mechanisms will reveal promising targets for development of more effective therapies.

[Experimental Detection Study on Cerebral Hemorrhage in Rabbits Based on Magnetic Induction Phase Shift Spectroscopy Under the Feature Band].

This study was aimed to improve the sensitivity of magnetic induction phase shift detection system for cerebral hemorrhage. In the study, a cerebral hemorrhage model with 13 rabbits was established by injection of autologous blood and the cerebral hemorrhage was detected by utilizing magnetic induction phase shift spectroscopy (MIPSS) detection method under the feature band. Sixty five groups of phase shift spectroscopy data were obtained. According to the characteristics of cerebral hemorrhage phase shift spectroscopy under the feature hand, an effective method, B-F distribution, to diagnose the severity of cerebral hemorrhage was designed. The results showed that using MIPSS detection method under feature band, the phase shift obviously growed with increase of injection volume of autologous blood, and the phase shift induced by a 3-mL injection reached -7.750 3 degrees ± 1.420 4 degrees. B-F distribution could effectively diagnose the severity of cerebral hemorrhage. It can be concluded that the sensitivity of the cerebral hemorrhage magnetic induction detection system is improved by one order of magnitude with the MIPSS detection method under the feature band.

Therapeutic targets and potential delivery systems of melatonin in osteoarthritis.

Osteoarthritis (OA) is a highly prevalent age-related musculoskeletal disorder that typically results in chronic pain and disability. OA is a multifactorial disease, with increased oxidative stress, dysregulated inflammatory response, and impaired matrix metabolism contributing to its onset and progression. The neurohormone melatonin, primarily synthesized by the pineal gland, has emerged as a promising therapeutic agent for OA due to its potential to alleviate inflammation, oxidative stress, and chondrocyte death with minimal adverse effects. The present review provides a comprehensive summary of the current understanding regarding melatonin as a promising pharmaceutical agent for the treatment of OA, along with an exploration of various delivery systems that can be utilized for melatonin administration. These findings may provide novel therapeutic strategies and targets for inhibiting the advancement of OA.

The research landscape of oxidative stress in osteoarthritis from 1998 to 2021: a systematic bibliometric analysis.

OBJECTIVE: A substantial body of literature pertaining to oxidative stress in osteoarthritis (OA) has been published over the past few decades. However, a comprehensive systematic analysis in this field is currently lacking. The objective of this study was to perform a bibliometric analysis to visualize the current research hotspots and evolving trends associated with oxidative stress in OA, in order to contribute to a more comprehensive understanding of this field. METHODS: The raw data pertaining to oxidative stress in OA, published between 1998 and 2021, were obtained from the Web of Science Core Collection database (WoSCC). In order to provide comprehensive results across multiple dimensions, various bibliometric software tools were employed to quantify and analyze the research focuses and trends regarding oxidative stress in OA. RESULTS: A total of 1178 original articles and reviews on oxidative stress in OA were included, with China and the USA emerging as the primary driving forces in this research field. Notably, Wenzhou Medical University stood out as the most prolific institution in terms of publication volume. Blanco FJ was the most prolific author, and the journal with the most publications was Osteoarthritis and Cartilage. The analysis of keyword burst detection revealed that the investigation of chondrocyte senescence induced by oxidative stress was the most frequent. CONCLUSION: The burgeoning body of literature pertaining to oxidative stress in OA has experienced a consistent growth over the past few decades, and this field will garner widespread attention and in-depth investigation. The frontier of chondrocyte senescence, as revealed by bibliometric analyses, represents a special focus of this field, with potential as a vital therapeutic target for OA.

Hypoxia inducible factor-1ɑ as a potential therapeutic target for osteosarcoma metastasis.

Osteosarcoma (OS) is a malignant tumor originating from mesenchymal tissue. Pulmonary metastasis is usually present upon initial diagnosis, and metastasis is the primary factor affecting the poor prognosis of patients with OS. Current research shows that the ability to regulate the cellular microenvironment is essential for preventing the distant metastasis of OS, and anoxic microenvironments are important features of solid tumors. During hypoxia, hypoxia-inducible factor-1α (HIF-1α) expression levels and stability increase. Increased HIF-1α promotes tumor vascular remodeling, epithelial-mesenchymal transformation (EMT), and OS cells invasiveness; this leads to distant metastasis of OS cells. HIF-1α plays an essential role in the mechanisms of OS metastasis. In order to develop precise prognostic indicators and potential therapeutic targets for OS treatment, this review examines the molecular mechanisms of HIF-1α in the distant metastasis of OS cells; the signal transduction pathways mediated by HIF-1α are also discussed.

Single-cell profiling and functional screening reveal crucial roles for lncRNAs in the epidermal re-epithelialization of human acute wounds.

Objectives: Re-epithelialization is an important physiological process for repairing skin barrier function during wound healing. It is primarily mediated by coordinated migration, proliferation, and differentiation of keratinocytes. Long noncoding RNAs (lncRNAs) are essential components of the noncoding genome and participate in various biological processes; however, their expression profiles and function in re-epithelialization during wound healing have not been established. Methods: We investigated the distribution of lncRNAs during wound re-epithelialization by comparing the genomic profiles of uninjured skin and acute wound (AW) from healthy donors. We performed functional screening of differentially expressed lncRNAs to identify the important lncRNAs for re-epithelialization. Results: The expression of multiple lncRNAs is changed during human wound re-epithelialization process. We identified VIM-AS1, SMAD5-AS1, and LINC02581 as critical regulators involved in keratinocyte migration, proliferation, and differentiation, respectively. Conclusion: LncRNAs play crucial regulatory roles in wound re-epithelialization. We established lncRNA expression profile in human acute wounds compared with intact skin, offering valuable insights into the physiological mechanisms underlying wound healing and potential therapeutic targets.

The sonic hedgehog pathway suppresses oxidative stress and senescence in nucleus pulposus cells to alleviate intervertebral disc degeneration via GPX4.

Disruption of intervertebral disc (IVD) homeostasis caused by oxidative stress and nucleus pulposus cell (NPC) senescence is a main cause of intervertebral disc degeneration (IDD). The sonic hedgehog (Shh) pathway plays an important role in IVD development, but its roles in IDD are unknown. This study aimed to investigate the effects of the Shh pathway on the alleviation of IDD and the related mechanisms. In vivo, the effect of the Shh pathway on IVD homeostasis was studied by intraperitoneal injection of recombinant Shh (rShh) and GANT61 based on puncture-induced IDD. GANT61, lentivirus-coated sh-Gli1 and rShh were used to investigate the role and mechanism of the Shh pathway in NPCs based on senescence induced by Braco19 and oxidative stress induced by TBHP. Shh pathway expression decreased, and senescence and oxidative stress increased with age. Intraperitoneal injection of rShh activated the Shh pathway to suppress oxidative stress and NPC senescence and consequently alleviated needle puncture-induced IDD. In vitro, the Shh pathway upregulated glutathione peroxidase 4 (GPX4) expression to suppress oxidative stress and senescence in NPCs. Moreover, GPX4 suppression in NPCs by si-GPX4 significantly reduced the protective effect of the Shh pathway on oxidative stress and senescence in NPCs. Our results demonstrate for the first time that the Shh pathway plays a key role in the alleviation of IDD by suppressing oxidative stress and cell senescence in NP tissues. This study provides a new potential target for the prevention and reversal of IDD.

Transformation of NSCLC to SCLC harboring EML4-ALK fusion with V1180L mutation after alectinib resistance and response to lorlatinib: A case report and literature review.

BACKGROUND: Histological transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) with anaplastic lymphoma kinase (ALK) positivity is extremely uncommon in ALK-positive NSCLC. To date, there have been limited reports regarding cases of SCLC transformation, and the optimal therapeutic strategies and prognosis for such patients remain unclear. This case is the first to describe the effectiveness of lorlatinib in treating a patient with SCLC that transformed from NSCLC harboring the ALK fusion V1180L mutation following acquired resistance to alectinib therapy. CASE DESCRIPTION: We present a case of alectinib-induced transformation from ALK-positive NSCLC to SCLC with an ALK V1180L mutation after acquiring alectinib resistance. The patient achieved disease remission with lorlatinib treatment following ineffective chemotherapy. In April 2022, a 53-year-old male was diagnosed with ALK-positive advanced poorly differentiated adenocarcinoma with neuroendocrine differentiation in the left lower lobe of the lung. The diagnosis was accompanied by multiple bone metastases and brain metastases, categorizing the stage as cT3N2M1. Following 8 months of alectinib treatment, chest computed tomography (CT) and cranial magnetic resonance imaging (MRI) revealed disease progression. Pathological and genetic analyses indicated the transformation to pulmonary small cell carcinoma accompanied by ALK fusion V1180L mutation. After the administration of two cycles of EP chemotherapy with unsatisfactory response, oral lorlatinib therapy was initiated. A subsequent month of treatment resulted in notable reduction of the left lung lesion according to chest CT, as well as a significant decrease in intracranial lesions based on cranial MRI. After taking lorlatinib for 5 months, the lesions continue to shrink, and there is a noticeable improvement in the patient's quality of life. Currently, the patient remains in a state of sustained improvement. CONCLUSION: This study affirms the efficacy of lorlatinib in patients with ALK-positive SCLC transformation harboring the V1180L mutation. Furthermore, it underscores the imperative of conducting genetic testing in patients who transition to SCLC following ALK-TKI resistance, as targeted therapies may remain efficacious if a genetic driver is identified.

Identification of EGFR as an essential regulator in chondrocytes ferroptosis of osteoarthritis using bioinformatics, in vivo, and in vitro study.

Objective: The mechanisms of chondrocytes ferroptosis in osteoarthritis (OA) have not yet been fully elucidated. This study aimed to identify key ferroptosis related genes (FRGs) involved in chondrocytes ferroptosis. Methods: LASSO, SVM-RFE, and receiver operating characteristic curve (ROC) were performed to screen key differentially expressed FRGs (DEFRGs). Functional analyses were conducted using GO, and KEGG analyses. Unsupervised clustering analysis was used to identify ferroptosis related patterns. The CeRNA network was constructed to predict the upstream miRNAs and lncRNAs. Finally, we validated the role of EGFR in chondrocytes ferroptosis using in vivo and in vitro experiments. Results: A total of 42 DEFRGs were identified between OA and normal cartilages. GO and KEGG analyses indicated that these DEFRGs were significantly engaged in ferroptosis related biological processes and pathways, such as cellular response to oxidative stress, positive regulation of programmed cell death, MAPK and PI3K-Akt signaling pathways. Moreover, four key DEFRGs, including ACSF2, AURKA, EGFR, and KLHL24, were considered as potential biomarkers of OA. Moreover, two distinct ferroptosis related patterns were determined, and a total of 882 differentially expressed genes were identified which might participate in extracellular matrix degradation and inflammatory response. In addition, the CeRNA network showed that EGFR could be competitively regulated by 3 lncRNAs and 4 miRNAs. Significantly, the expression of EGFR was downregulated in human OA cartilages, OA mouse model, and erastin induced chondrocytes. EGFR inhibition could induce the occurrence of chondrocytes ferroptosis and ECM degradation which could be reversed by the addition of Ferrostatin-1. Conclusion: Our study has identified ACSF2, AURKA, EGFR, and KLHL24 as ferroptosis-related biomarkers in OA. Furthermore, we have conducted a preliminary investigation into the role of EGFR in regulating chondrocytes ferroptosis. These findings offer novel insights into the molecular mechanisms underlying OA.

Study of the Immediately Detection of Mild Traumatic Brain Injury by Feature Engineering on Electroencephalography.

The electroencephalographic (EEG) diagnosis of mild traumatic brain injury (mTBI) is not usually timely, and the detection is often performed several hours or days after the trauma, leading to a decrease in the accuracy of its detection. In this study, EEG signals are recorded immediately after mTBI by connecting a bipolar single lead to injured animals. And three types of EEG features, namely time domain, frequency domain, and nonlinear dynamics, are screened for optimal feature subset in mTBI detection. First, EEG signals of animals are recorded before and after establishing the animal model of mTBI. Second, signal preprocessing, feature extraction, and feature preprocessing are performed to obtain the full-feature dataset, and 1442 feature subsets are obtained by 15 feature reduction algorithms extracted from combinations of 47 features. Ultimately, the support vector machines and K-nearest neighbor algorithms are trained and tested respectively, and their performance is comprehensively compared to determine the optimal feature subset for mTBI detection. In the EEG dataset collected in this study, a total of eight feature subsets extracted from combinations of original 47 features and classification models with 100% accuracy are obtained. This study shows the perspective of immediately detecting mTBI based on a bipolar single-lead EEG.

A Roadmap for a Consensus Human Skin Cell Atlas and Single-Cell Data Standardization.

Single-cell technologies have become essential to driving discovery in both basic and translational investigative dermatology. Despite the multitude of available datasets, a central reference atlas of normal human skin, which can serve as a reference resource for skin cell types, cell states, and their molecular signatures, is still lacking. For any such atlas to receive broad acceptance, participation by many investigators during atlas construction is an essential prerequisite. As part of the Human Cell Atlas project, we have assembled a Skin Biological Network to build a consensus Human Skin Cell Atlas and outline a roadmap toward that goal. We define the drivers of skin diversity to be considered when selecting sequencing datasets for the atlas and list practical hurdles during skin sampling that can result in data gaps and impede comprehensive representation and technical considerations for tissue processing and computational analysis, the accounting for which should minimize biases in cell type enrichments and exclusions and decrease batch effects. By outlining our goals for Atlas 1.0, we discuss how it will uncover new aspects of skin biology.

Worldwide survey on implantation of and outcomes for conduction system pacing with His bundle and left bundle branch area pacing leads.

BACKGROUND: Adoption and outcomes for conduction system pacing (CSP), which includes His bundle pacing (HBP) or left bundle branch area pacing (LBBAP), in real-world settings are incompletely understood. We sought to describe real-world adoption of CSP lead implantation and subsequent outcomes. METHODS: We performed an online cross-sectional survey on the implantation and outcomes associated with CSP, between November 15, 2020, and February 15, 2021. We described survey responses and reported HBP and LBBAP outcomes for bradycardia pacing and cardiac resynchronization CRT indications, separately. RESULTS: The analysis cohort included 140 institutions, located on 5 continents, who contributed data to the worldwide survey on CSP. Of these, 127 institutions (90.7%) reported experience implanting CSP leads. CSP and overall device implantation volumes were reported by 84 institutions. In 2019, the median proportion of device implants with CSP, HBP, and/or LBBAP leads attempted were 4.4% (interquartile range [IQR], 1.9-12.5%; range, 0.4-100%), 3.3% (IQR, 1.3-7.1%; range, 0.2-87.0%), and 2.5% (IQR, 0.5-24.0%; range, 0.1-55.6%), respectively. For bradycardia pacing indications, HBP leads, as compared to LBBAP leads, had higher reported implant threshold (median [IQR]: 1.5 V [1.3-2.0 V] vs 0.8 V [0.6-1.0 V], p = 0.0008) and lower ventricular sensing (median [IQR]: 4.0 mV [3.0-5.0 mV] vs. 10.0 mV [7.0-12.0 mV], p < 0.0001). CONCLUSION: In conclusion, CSP lead implantation has been broadly adopted but has yet to become the default approach at most surveyed institutions. As the indications and data for CSP continue to evolve, strategies to educate and promote CSP lead implantation at institutions without CSP lead implantation experience would be necessary.

Factor analysis and mechanism disclosure of supercritical CO2 filtration behavior in tight shale reservoirs.

As an important working fluid in tight shale reservoir, supercritical CO2 has been proven to improve oil recovery efficiently. However, the high filtration caused by the low viscosity of pure supercritical CO2 hinders its development. The research objective of this investigation is to explore the filtration of supercritical CO2 with a branched siloxane (BTMT) as a CO2 thickener and filtration-reducing agent, and analyze the influence level of some parameters about rock core and chemicals on the CO2 filtration in the tight shale reservoir by using response surface method (RSM). The results demonstrate that the rising temperature causes a gradually increasing filtration, but filtration coefficient (f) decreases with increasing the pressure difference P, injection speed, and thickener concentration. The thickener concentration is the factor that causes the greatest change in filtration coefficient according to the response surface method, and the injection speed has the smallest effect on the filtration. The viscosity of fracturing fluid is the main characterization parameter leading to change of filtration coefficient, all factors that contribute to increasing the viscosity of the fracturing fluid will lead to a reduction in the filtration coefficient and an enhanced oil recovery. In addition, the adsorption and reservoir residue of BTMT on low-permeability shale were subordinated to a Langmuir monolayer theory, and a low residual of BTMT in shale can prevent thickeners and fracturing fluids from damaging shale reservoirs. The improvement of thickener and CO2 fracturing technology provided a basic reference for shale exploitation, greenhouse effect, and reservoir protection.

Beyond the Code: Noncoding RNAs in Skin Wound Healing.

An increasing number of noncoding RNAs (ncRNAs) have been found to regulate gene expression and protein functions, playing important roles in diverse biological processes and diseases. Their crucial functions have been reported in almost every cell type and all stages of skin wound healing. Evidence of their pathogenetic roles in common wound complications, such as chronic nonhealing wounds and excessive scarring, is also accumulating. Given their unique expression and functional properties, ncRNAs are promising therapeutic and diagnostic entities. In this review, we discuss current knowledge about the functional roles of noncoding elements, such as microRNAs, long ncRNAs, and circular RNAs, in skin wound healing, focusing on in vivo evidence from studies of human wound samples and animal wound models. Finally, we provide a perspective on the outlook of ncRNA-based therapeutics in wound care.

Circular RNA Signatures of Human Healing and Nonhealing Wounds.

Venous ulcers (VUs) have complex and obscure pathogenicity, and effective VU therapies are still lacking. Circular RNAs (circRNAs) have emerged as powerful gene regulators with important roles in health and disease. In this study, we used paired total RNA and small RNA sequencing to profile circRNAs, protein-coding mRNAs, and microRNAs expression in a unique collection of clinical samples: healthy skin and acute wounds at inflammatory and proliferative phases and wound-edge VU biopsies. We unravel a dynamically changed expression pattern of circRNAs during human skin repair and their abnormal expression signature in VU, which are presented as a searchable web resource (www.xulandenlab.com/humanwounds-circrna). We analyzed the coexpression relationship between the circRNAs and mRNAs with weighted correlation network analysis and constructed circRNA‒mRNA‒microRNA networks. This allowed us to expose the regulatory networks specific to the inflammatory and proliferative phases of wound repair and VU, the biological processes the circRNAs may regulate, and the circRNAs that could sponge microRNAs in human wounds. Importantly, we found that hsa-CHST15_0003 and hsa-TNFRSF21_0001, two circRNAs upregulated in VU, hampered epidermal keratinocyte migration while promoting proliferation by modulating gene networks underpinning these cellular processes. This study paves the way to decipher the functional significance of circRNAs in tissue repair.