RAB6A functions as a critical modulator of the stem-like subsets in cholangiocarcinoma.

RAB6A is a member of RAB GTPase family and plays an important role in the targeted transport of neurotrophic receptors and inflammatory cytokines. RAB6A-mediated secretory pathway is involved in many physiological and pathological processes. Defects in RAB6A-mediated secretory pathway may lead to the development of many diseases, including cancer. However, its role in cholangiocarcinoma (CCA) has not yet been revealed. We explored the regulatory role of RAB6A in the stem-like subsets of CCA. We showed that RAB6A knockdown (KD) impedes cancer stem cells (CSCs) properties and epithelial-mesenchymal transition in vitro and that suppression of RAB6A inhibits tumor growth in vivo. We screened target cargos of RAB6A in CCA cells and identified a extracellular matrix component as the target cargo. RAB6A binds directly to OPN, and RAB6A KD suppressed OPN secretion and inhibited the interaction between OPN and αV integrin receptor. Moreover, RAB6A KD inhibited the AKT signaling pathway, which is a downstream effector of the integrin receptor signaling. In addition, shRNA targeting OPN blocked endogenous expression of OPN and consequently weakened CSCs properties in RAB6A-formed spheres. Similarly, inhibitor of AKT signaling, MK2206 also impedes oncogenic function of RAB6A in the stem-like subsets of CCA cells. In conclusion, our findings showed that RAB6A sustains CSCs phenotype maintenance by modulating the secretion of OPN and consequentially activating the downstream AKT signaling pathway. Targeting the RAB6A/OPN axis may be an effective strategy for CCA therapy.

FBXO31 sensitizes cancer stem cells-like cells to cisplatin by promoting ferroptosis and facilitating proteasomal degradation of GPX4 in cholangiocarcinoma.

BACKGROUND & AIMS: Cholangiocarcinoma (CCA) is a malignant tumour originating from the biliary epithelium that easily infiltrates, metastasizes and recurs. The deficiency of FBXO31 facilitates the initiation and progression of several types of cancer. However, the involvement of FBXO31 in CCA progression has remained unclear. METHODS: qRT-PCR was used to detect the expression of FBXO31 in CCA. The biological functions of FBXO31 were confirmed in vivo and in vitro. Sphere formation and flow cytometry were used to identify the stem cell properties of CCA. RESULTS: FBXO31 is downregulated in CCA and that deficiency of FBXO31 is associated with the TNM stage of CCA. Functional studies showed FBXO31 inhibits cell growth, migration, invasion, cancer stem cell (CSC) properties and epithelial-mesenchymal transition (EMT) in vitro and impedes tumour growth in vivo. In addition, overexpression of FBXO31 increases the cisplatin (CDDP) sensitivity of CCA cells. RNA-sequencing analysis revealed that FBXO31 is involved in redox biology and metal ion metabolism in CCA cells during CDDP treatment. Further studies revealed that FBXO31 enhances ferroptosis induced by CDDP in CCA and CSC-like cells. FBXO31 enhances ubiquitination of glutathione peroxidase 4 (GPX4), which leads to proteasomal degradation of GPX4. Moreover, overexpression of GPX4 compromises the promoting effects of FBXO31 on CDDP-induced ferroptosis in CCA and CSC-like cells. CONCLUSIONS: Our studies indicate that FBXO31 functions as a tumour suppressor in CCA and sensitizes CSC-like cells to CDDP by promoting ferroptosis and facilitating the proteasomal degradation of GPX4.

Psychological Symptoms and Posttraumatic Growth Among the General Population in Wuhan, China During the COVID-19 Pandemic: A Cross-Sectional Study.

The aim of the current study was to investigate psychological symptoms and post-traumatic growth (PTG) among the general population in Wuhan, China during the coronavirus disease 2019 (COVID-19) pandemic. An online survey was conducted using convenience sampling. Participants were invited to fill out this questionnaire, which included information on sociodemographic characteristics and other survey objectives. The Psychological Questionnaire for Emergent Events of Public Health (PQEEPH) and the Chinese version of the Posttraumatic Growth Inventory (PTGI) were used. The prevalence of depression, neurasthenia, fear, obsessive-anxiety, and hypochondriasis among 311 participants were 61.1%, 69.8%, 97.8%, 57.2%, and 45%, respectively. Results indicated that a substantial proportion of the general population may have experienced psychological symptoms as well as PTG, due to the COVID-19 pandemic. Findings demonstrate the importance of developing targeted psychological interventions for those at risk for mental health symptoms. [Journal of Psychosocial Nursing and Mental Health Services, 60(4), 39-46.].

Effect of quadratus lumborum block on postoperative cognitive function in elderly patients undergoing laparoscopic radical gastrectomy: a randomized controlled trial.

BACKGROUND: Quadratus lumborum block (QLB) is a novel and effective postoperative analgesia method for abdominal surgeries. However, whether QLB can affect early postoperative cognitive function by inhibiting surgical traumatic stress and the inflammatory response remains unclear. This study aimed to explore the effect of QLB on postoperative cognitive function in elderly patients undergoing laparoscopic radical gastrectomy. METHODS: Sixty-four elderly patients who underwent laparoscopic radical gastrectomy were randomly divided into the QLB group (Q group, n = 32) and control group (C group, n = 32). The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to measure cognitive function 1 day before and 7 days after surgery. Postoperative cognitive dysfunction (POCD) was defined as a decline of ≥ 1 SD in both tests. The visual analog scale (VAS) scores 6 h (T1), 24 h (T2), and 48 h (T3) after surgery were measured. The serum levels of high mobility group box protein 1 (HMGB1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were evaluated 1 day before surgery (baseline), and 1 day (day 1) and 3 days after surgery (day 3). The intraoperative remifentanil dosage, sufentanil consumption 24 h after surgery, recovery time from anesthesia, and adverse effects were also compared. RESULTS: POCD was present in two patients in the QLB group and eight patients in the C group 7 days after surgery (6.7 % vs. 27.6 %, P = 0.032). The MMSE and MoCA scores were similar in both groups preoperatively, and the two scores were higher in the QLB group than in the C group 7 days after surgery (P < 0.05). The VAS scores were significantly lower in the Q group at all times after surgery (P < 0.05). Compared with the C group, the levels of HMGB1, TNF-α, and IL-6 were significantly decreased 1 and 3 days after surgery in the QLB group (P < 0.05). The remifentanil consumption intraoperatively and sufentanil 24 h postoperatively were significantly lower in the QLB group (P < 0.05). The recovery time from anesthesia was shorter in the QLB group (P < 0.05). No severe adverse effects occurred in either group. CONCLUSIONS: QLB could improve postoperative cognitive function in elderly patients undergoing laparoscopic radical gastrectomy. This may be related to the suppression of the inflammatory response after surgery. TRIAL REGISTRATION: Chictr.org.cn identifier ChiCTR1900027574 (Date of registry: 19/11/2019, prospectively registered).

FBXO31 modulates activation of hepatic stellate cells and liver fibrogenesis by promoting ubiquitination of Smad7.

Liver fibrosis is a critical pathological process in the early stage of many liver diseases, including hepatic cirrhosis and liver cancer. However, the molecular mechanism is not fully revealed. In this study, we investigated the role of F-box protein 31 (FBXO31) in liver fibrosis. We found FBXO31 upregulated in carbon tetrachloride (CCl4 ) induced liver fibrosis and in activated hepatic stellate cells, induced by transforming growth factor-ß (TGF-ß). The enforced expression of FBXO31 caused enhanced proliferation and increased expression of α-smooth muscle actin (α-SMA) and Col-1 in HSC-T6 cells. Conversely, suppression of FBXO31 resulted in inhibition of proliferation and decreased accumulation of α-SMA and Col-1 in HSC-T6 cells. In addition, upregulation of FBXO31 in HSC-T6 cells decreased accumulation of Smad7, the negative regulator of the TGF-ß/smad signaling pathway, and suppression of the FBXO31 increased accumulation of Smad7. Immunofluorescence staining showed FBXO31 colocalized with Smad7 in HSC-T6 cells and in liver tissues of BALB/c mice treated with CCl4 . Immunoprecipitation demonstrated FBXO31 interacted with Smad7. Moreover, FBXO31 enhanced ubiquitination of Smad7. In conclusion, FBXO31 modulates activation of HSCs and liver fibrogenesis by promoting ubiquitination of Smad7.

Analgesic effect of the ultrasound-guided subcostal approach to transmuscular quadratus lumborum block in patients undergoing laparoscopic nephrectomy: a randomized controlled trial.

BACKGROUND: Quadratus lumborum block (QLB) is an effective analgesia that lowers opioid consumption after lower abdominal and hip surgeries. The subcostal approach to transmuscular QLB is a novel technique that can provide postoperative analgesia by blocking more dermatomes. The aim of this study is to evaluate the efficacy and viability of subcostal approach to QLB after laparoscopic nephrectomy. METHODS: Sixty patients who underwent laparoscopic nephrectomy were randomly divided into the subcostal approach to QLB group (QLB group, n = 30) and the control group (C group, n = 30). All patients underwent ultrasound-guided subcostal approach to QLB in an ipsilateral parasagittal oblique plane at the L1-L2 level. The QLB group received 0.4 cc/kg of 0.3% ropivacaine, and the C group received 0.4 cc/kg of 0.9% saline. Postoperatively, a patient-controlled intravenous analgesic pump with sufentanil was attached to all the patients. The primary outcome was sufentanil consumption within the first 24 h after surgery. The secondary outcomes included the Ramsey sedation scale (RSS) scores and Bruggemann comfort scale (BCS) scores 6 h (T1), 12 h (T2), and 24 h (T3) after surgery, intraoperative remifentanil consumption, number of patients requiring rescue analgesia, time to recovery of intestinal function, mobilization time after surgery, and presence of side effects. RESULTS: Sufentanil consumption within the first 24 h after surgery was significantly lower in the QLB group than in the C group (mean [standard deviation]: 34.1 [9.9] µg vs 42.1 [11.6] µg, P = .006). The RSS scores did not differ between the two groups, and the BCS scores of the QLB group at T1 and T2 time points was significantly higher than those of the C group(P<0.05). The consumption of remifentanil intraoperatively and the number of patients requiring rescue analgesia were significantly lower in the QLB group (P<0.05). Time to recovery of intestinal function and mobilization time after surgery were significantly earlier in the QLB group (P<0.05). The incidence of postoperative nausea and vomiting was significantly lower in the QLB group (P<0.05). CONCLUSIONS: The ultrasound-guided subcostal approach to QLB is an effective analgesic technique in patients undergoing laparoscopic nephrectomy as it reduces the consumption of sufentanil postoperatively. TRIAL REGISTRATION: ChiCTR1800020296 0 (Prospective registered). Initial registration date was 22/12/2018.

Improved Photocatalytic Hydrogen Production Performance Over NaTaO3/Reduced Graphene Oxide Composite Photocatalyst.

NaTaO3/reduced graphene oxide (RGO) composite were prepared via a two-step hydrothermal method. The as-prepared NaTaO3/RGO composite were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), UV-Vis diffuse reflectance spectra (DRS), photoluminescence spectra (PL) and X-ray photoelectron spectroscopy (XPS). The results indicated the reduction of graphene oxide and the chemical bonding between RGO and NaTaO3 are achieved simultaneously. As a result, NaTaO3/RGO composite possessed efficient charge separation properties. Hence, in the photocatalytic measurement toward the H2 production from an aqueous Na2S/Na2SO3 solution under UV illumination, a significant improvement in the H2 production rate was observed over NaTaO3/RGO composite, compared to the pure NaTaO3 and mechanically mixed NaTaO3-RGO composite with the same RGO content. In particular, the photocatalytic H2 production rate over NaTaO3/2%RGO with RGO content of 2 wt% was 3.82 times higher than that of pure NaTaO3. Moreover, the photocatalytic hydrogen production performance of NaTaO3/2%RGO was rather stable. A plausible electron transfer mechanism was proposed to discuss the improved photocatalytic H2 production performance.

MiR-4673 Modulates Paclitaxel-Induced Oxidative Stress and Loss of Mitochondrial Membrane Potential by Targeting 8-Oxoguanine-DNA Glycosylase-1.

BACKGROUND: Our previous study identified a novel microRNA, miR-4673, which is upregulated in A549 cells exposed to paclitaxel (PTX). In this study, we investigated the role of miR-4673 in PTX-induced cytotoxicity. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, apoptosis assay, 5,5',6,6'-Tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide (JC-1) staining and 2',7'-Dichlorofluorescein (DCFH) staining were used to evaluate cell viability, apoptosis, mitochondrial membrane potential (MMP) loss and reactive oxygen species (ROS) generation in A549 and H1299 cells. Bioinformatics analysis and Luciferase reporter assay were used to explore whether 8-oxoguanine-DNA glycosylase-1 (OGG1) is a target gene of miR-4673. RESULTS: Enforced expression of miR-4673 decreased cell viability and increased PTX-induced apoptosis, MMP loss and reactive oxygen species (ROS) generation in A549 and H1299 cells. Bioinformatics analysis, which was used to identify potential target of miR-4673, revealed a binding site of miR-4673 in 3'UTR of OGG1. Luciferase reporters assays showed that miR-4673 specifically binds to 'CUGUUGA' in 3'UTR of OGG1. Enforced expression of miR-4673 decreased accumulation of OGG1. In addition, silencing OGG1 enhanced inhibitory effects of PTX on apoptosis, MMP loss and ROS generation, which is similar to effects of miR-4673. Moreover, enforced expression of OGG1 compromised promoting effects of miR-4673 on PTX-induced apoptosis, MMP loss and ROS generation. CONCLUSION: miR-4673 modulates PTX-induced apoptosis, MMP loss and ROS generation by targeting OGG1.

Continuity of Care to Prevent Readmissions for Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

Readmissions of patients with chronic obstructive pulmonary disease (COPD) to hospitals cast a heavy burden to health care systems. This meta-analysis was aimed to assess the efficacy of continuity of care as interventions, which reduced readmission and mortality rates of such patients. PubMed, Cochrane Library and Embase were searched for articles published before July 2015. A total of 31 reports with randomized controlled trials (RCTs) were finally included in this meta-analysis. The results showed that health education reduced all-cause readmission at 3 months. In addition, health education, comprehensive nursing intervention (CNI) and telemonitoring reduced all-cause readmissions over 6-12 months, and the effect of CNI was best because CNI also reduced COPD-specific readmissions. Home visits also reduced COPD-specific readmissions (the quality more than moderate), but it did not reduce the risk for all-cause readmissions (risk ratios (RRs), 0.92 [95% CI, 0.82-1.04]; moderate quality). There was no statistically significant difference in reducing mortality and quality of life (QOL) among various continued cares. In conclusion, CNI, telemonitoring, health education and home visits should receive more consideration than other interventions by caregivers seeking to implement continued care interventions for patients with COPD.

Abnormal miRNA-30e Expression is Associated with Breast Cancer Progression.

BACKGROUND: microRNAs (miRNAs) are involved in the regulation of various cellular processes, such as differentiation, proliferation, metabolism, and apoptosis, and they have been implicated in several diseases, including cancers. METHODS: To assess the role of miRNA in the progression of breast cancer, we performed TaqMan-based miRNA profiling for plasma from patients with breast cancer (n = 53), unrelated diseases (n = 40), or matched healthy controls (n = 40), and for breast tumors or adjacent non-tumors (n = 41). RESULTS: We selected 18 miRNAs with predicted roles in breast cancer and demonstrated that let-7i (p = 0.019), let-7a (p = 0.02), and miR-650 (p = 0.008) were significantly up-regulated in plasma; miR-21 (p < 0.001) is up-regulated in breast cancer tissue, and miR-30e was down-regulated in both plasma (p < 0.001) and breast cancer tissues (p = 0.004). Plasma miR-30e expression was shown to be statistically associated with age (p = 0.0402) and clinical stage (p = 0.007). However, receiver-operating characteristic curve analyses suggested that miR-30e expression cannot significantly differentiate breast cancer from healthy tissue or plasma. Consistent with a potential role for miR-30e in breast cancer, three predicted targets of miR-30e (RAB11A, BNIP3L, and RAB32) are up-regulated in breast cancer tissue. CONCLUSIONS: These findings suggest that reduced miR-30e correlates with the clinical stage of breast cancer. It is worthwhile to further explore that the potential role of miR-30e as a tumor suppressor in breast cancer, as well as its potential therapeutic utility.

Pro-inflammatory response and oxidative stress induced by specific components in ambient particulate matter in human bronchial epithelial cells.

Previous studies have shown that biological effect of particulate matter (PM2.5) is involved in including chemical composition and mass concentration, but the precise components and biological action on human bronchial epithelial cell line (BEAS-2B) are still unclear. The aim of this study was to evaluate the in vitro toxicity of PM2.5 collected at six urban sites in China, and to investigate how particle composition affects cytotoxicity. We used human bronchial epithelial (BEAS-2B) cell lines as model in vitro to expose to PM2.5 from different source, and then reactive oxygen species (ROS), superoxide dismutase activity and total antioxidant capacity were analyzed. Furthermore, we estimated the polycyclic aromatic hydrocarbon (PAH) and transition metal and the endotoxin contents. The mRNA expression of IL-1ß and IL-10 following exposure to PM2.5 was measured by QRT-PCR. We also observed the mitochondrial membrane potential (MMP) using JC-1 staining, and apoptosis of BEAS-2B using flow cytometry. In addition, double-stranded DNA breaks (DSBs) were assessed using γ-H2AX immunofluorescence. Our results show that high concentrations of PAHs and elemental Ni were strongly associated with high apoptosis rates and high expression of IL-1ß, in addition, Fe element was associated with the ROS level, furthermore, Fe and Cr element were associated with DNA damage in BEAS-2B cells. The cytotoxic effects of urban PM2.5 derived from six different cities in China appear dependent on the specific components in each. Our results indicate that air quality standards based on PM2.5 components may be more relevant than concentration-response functions (CRF). © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 923-936, 2016.

Effects of radiotherapy on nasopharyngeal carcinoma cell invasiveness.

Radiotherapy is widely used in the treatment of nasopharyngeal carcinoma (NPC), whereas its effects on the NPC growth, survival, and metastases have not been completely evaluated. Here, we compared the detected metastatic NPC tissues after radiotherapy (m-NPC) to the resected primary NPC tissues prior to radiotherapy (p-NPC). We detected higher levels of Snail2 protein, but not mRNA in m-NPC, compared to p-NPC. In vitro, a modest irradiation on NPC cells resulted in significant cell death, but increased Snail2 protein, but mRNA levels in the surviving NPC cells. Bioinformatics analyses showed that miR-613, which was significantly decreased in NPC cells after irradiation, targeted the 3'-UTR of Snail2 mRNA to inhibit its translation. Moreover, miR-613 overexpression inhibited Snail2-mediated cell invasiveness, while miR-613 depletion increased Snail2-mediated cell invasiveness in NPC cells. Finally, we detected significantly lower levels of miR-613 in m-NPC, compared to p-NPC. Together our data suggest that although radiotherapy induced NPC cell death, it may increase Snail2-mediated NPC cell invasiveness through downregulating miR-613.

Mitochondrial OGG1 protects against PM2.5-induced oxidative DNA damage in BEAS-2B cells.

The enzyme 8-oxoguanine glycosylase 1 (OGG1) has been shown to be involved in the repair of oxidative DNA damage. However, the effect of OGG1 on oxidative DNA damage caused by particulate matter 2.5 (PM2.5) is unknown. Herein, we demonstrated that OGG1 could inhibit the generation of ROS and alleviate mitochondrial dysfunction and increased the expression of IL-1ß caused by PM2.5. The dichlorodihydrofluorescein diacetate (DCFH-DA) staining and 5,5',6,6'-tetrachloro-1,1',3,3'-. tetraethylbenzi-midazolylcarbocyanine iodide (JC-1) staining using flow cytometry showed that PM2.5 induces the generation of ROS and leads to a reduction in mitochondrial membrane potential (MMP) in BEAS-2B cells. Overexpression of OGG1 inhibited the generation of ROS and the decline in MMP. Knockdown of OGG1 by RNA interference (RNAi) increased the generation of ROS and reduced the MMP. Real-time quantitative PCR (RT-qPCR) for the mitochondrial DNA copy number (mtDNAcn) and flow cytometry for apoptosis revealed that OGG1 inhibits the apoptosis and decreases mtDNAcn induced by PM2.5. Additionally, the results of the comet assay showed that OGG1 had a significant repair effect on DNA strand breaks caused by PM2.5. Overexpression of OGG1 also significantly suppressed the expression of IL-1ß caused by PM2.5. Together, these data suggest that PM2.5 leads to mitochondrial dysfunction and the up-regulation of IL-1ß could be reversed by overexpression of OGG1. The mitochondrial dysfunction caused by PM2.5 could be relieved by OGG1. Thus, the base excision repair enzyme OGG1 may alleviate mitochondrial dysfunction caused by PM2.5 involved in the expression of IL-1ß.

Circulating microRNA Signatures Associated with Childhood Asthma.

BACKGROUND: MicroRNAs (miRNAs) exist stably and reproducibly in plasma and may be used as biomarkers for various diseases. Little is known about circulating miRNAs in the peripheral blood of juvenile patients with asthma. METHODS: In this study, we used hybridization arrays to compare the miRNA expression profiles among 6 juvenile patients with or without asthma. Using quantitative PCR (qPCR), we verified the expression levels of these miRNAs in plasma from patients with asthma (n = 40) and healthy subjects (n = 14). RESULTS: Our results showed that the levels of plasma miR-Let7C, miR-486, and miR-1260a in childhood asthma patients were significantly higher than in healthy controls (p < 0.01). Additionally, miR-1260a is correlated with the treatment schedule of these patients and patients with long treatment times had higher expression of miR-1260a than short treatment times; miR494 was significantly associated with challenge, and miR-3162-3p was significantly associated with MEF25 in asthma patients suggesting a potential correlation of miRNA levels with clinical disease parameters. Receiver operator characteristic analysis confirmed that the levels of miR-3162-3p could be used to discriminate childhood asthma patients from healthy subjects (area under the curve of 0.821), suggesting it may be a potential diagnostic biomarker. CONCLUSIONS: These results indicate that circulating miR-3162-3p and miR-1260a should be further evaluated as potential non-invasive biomarkers in diagnosis and treatment for childhood asthma.

Multifunctional nanoparticles as nanocarrier for vincristine sulfate delivery to overcome tumor multidrug resistance.

Multifunctional nanoparticles, Fol/R7 NPs, based on pH-sensitive PLGA-PEG-folate and cell penetrating peptide R7-conjugated PLGA-PEG, were constructed for targeting vincristine sulfate (VCR) to tumor and overcoming multidrug resistance (MDR). In this study, the pH-triggered VCR release was 65.6% during 8 h in pH 5.0, but only 35.8% in pH 7.4, demonstrating that a large amount of VCR released rapidly at weak acidic environment. The VCR-Fol/R7 NPs could significantly enhance cellular uptake and cytotoxicity in MCF-7 and MCF-7/Adr cells when compared to the nanoparticles solely modified by folate or R7. With folate receptor-mediated endocytosis and strong intracellular penetration, VCR-Fol/R7 NPs increased drug accumulation in resistant tumor cells by escaping P-glycoprotein mediated drug efflux. In vivo imaging suggested the active targeting attributed to pH sensitivity and folate receptor-mediated effect could improve tumor targeting efficacy. Indeed, VCR-Fol/R7 NPs exhibited the stongest antitumor efficacy in vivo. Therefore, Fol/R7 NPs are an effective nanocarrier for delivering antitumor drug and overcoming multidrug resistance.

SFRP2 modulates functional phenotype transition and energy metabolism of macrophages during diabetic wound healing.

Diabetic foot ulcer (DFU) is a serious complication of diabetes mellitus, which causes great health damage and economic burden to patients. The pathogenesis of DFU is not fully understood. We screened wound healing-related genes using bioinformatics analysis, and full-thickness skin injury mice model and cellular assays were used to explore the role of target genes in diabetic wound healing. SFRP2 was identified as a wound healing-related gene, and the expression of SFRP2 is associated with immune cell infiltration in DFU. In vivo study showed that suppression of SFRP2 delayed the wound healing process of diabetic mice, impeded angiogenesis and matrix remodeling, but did not affect wound healing process of control mice. In addition, suppression of SFRP2 increased macrophage infiltration and impeded the transition of macrophages functional phenotypes during diabetic wound healing, and affected the transcriptome signatures-related to inflammatory response and energy metabolism at the early stage of wound healing. Extracellular flux analysis (EFA) showed that suppression of SFRP2 decreased mitochondrial energy metabolism and increased glycolysis in injury-related macrophages, but impeded both glycolysis and mitochondrial energy metabolism in inflammatory macrophages. In addition, suppression of SFRP2 inhibited wnt signaling-related genes in macrophages. Treatment of AAV-SFRP2 augmented wound healing in diabetic mice and demonstrated the therapeutic potential of SFRP2. In conclusions, SFRP2 may function as a wound healing-related gene in DFU by modulating functional phenotype transition of macrophages and the balance between mitochondrial energy metabolism and glycolysis.

O-GlcNAcylation of CSNK2A1 by OGT is Involved in the Progression of Colorectal Cancer.

Colorectal cancer (CRC) metastasis is challenging for improved clinical outcomes. The casein kinase 2 alpha 1 (CSNK2A1) is an oncogene involved in several cancers. This study aimed to investigate the influence of CSNK2A1 on CRC progression and the related molecular mechanism. The CSNK2A1 levels were predicted using bioinformatic analysis and were measured using quantitative real-time polymerase chain reaction (qRT-PCR). Cell phenotypes were analyzed using cell-counting kit-8, colony formation, transwell assay, and western blot. Tumor growth was evaluated in a tumor-bearing mouse model in vivo. Similarly, O-GlcNAc modification of CSNK2A1 was assessed by immunoprecipitation, western blot, and immunofluorescence. Results indicated that CSNK2A1 was upregulated in CRC and was related to poor prognosis. Interference with CSNK2A1 suppressed CRC cell proliferation, migration, invasion, and epithelial-mesenchymal transition, inhibiting tumor growth. Moreover, OGT promoted the glycosylation modification of CSNK2A1, enhanced its protein stability, and reversed tumor progression when CSNK2A1 was knocked down. The CSNK2A1 might also affect CRC progression via the PI3K/AKT pathway. In conclusion, the OGT-O-GlcNAcylation-CSNK2A1 axis accelerated the malignant advancement of CRC, suggesting potential CRC therapeutic targets.

High-contrast and narrow-linewidth resonant profile for continuous operation atomic clock.

We report a high-contrast and narrow-linewidth resonant line profile by measuring the magneto-optical rotation of the transmitted light in a forward-scattering arrangement. We also report the splitting of the transmitted line profile at a strong microwave excitation. This profile may provide a good competitive scheme for the passive Rb frequency standard.

Positive response to niraparib in chemo-refractory patients with metastatic appendiceal mucinous adenocarcinoma harboring ATM mutations: A case report.

Background: Appendiceal mucinous adenocarcinoma, one kind of specific colorectal cancer, is lowly prevalent and rarely diagnosed in clinical practice. In addition, there have been limited standard treatment strategies established for patients with appendiceal mucinous adenocarcinoma, especially with metastatic disease. The regimens for colorectal cancer, which were adopted in appendiceal mucinous adenocarcinoma, usually resulted in limited effectiveness. Case presentation: Herein, we presented a case of chemo-refractory patient with metastatic appendiceal mucinous adenocarcinoma harboring ATM pathological mutation of exon 60, c.8734del, p.R2912Efs*26, and who has achieved a persistent response to salvage treatment of niraparib, with disease control time that reached 17 months and still in extension. Conclusions: We supposed that appendiceal mucinous adenocarcinoma patients harboring ATM pathological mutations may respond to the treatment of niraparib, even without a homologous recombination deficiency (HRD) status; however, it needs further confirmation in a larger cohort.

Chain mediations of perceived social support and emotional regulation efficacy between role stress and compassion fatigue: insights from the COVID-19 pandemic.

Background: Nurses at the frontline faced high risks of the COVID-19 infection, undertook heavy workloads of patient care, and experienced tremendous stress that often led to compassion fatigue. Aim: This study was to explore the role of positive psychosocial resources (i.e., perceived social support and emotional regulation efficacy) in the relationship between role stress and compassion fatigue. Methods: A cross-sectional design was conducted in Hubei Province, China between May and September 2021. The Role Stress Questionnaire, the Perceived Social Support Scale, the Emotional Regulation Efficacy Scale, and the Professional Quality of Life Scale were used to measure key variables of interest. Nurse socio-demographic data were also collected. Structural equation modeling was used to explore the relationships, including potential mediating effect, among role stress, perceived social support, emotional regulation efficacy, and compassion fatigue. Results: A total of 542 nurses participated in this investigation, and 500 were eventually enrolled in the analysis. The incidence of compassion fatigue among nurses was 94.2%, including 65.8% of nurses reporting at least moderate compassion fatigue. Univariate analysis showed that educational level, marital status, hospital rank, sleep time were the factors affecting compassion fatigue of the nurses. The structural equation modeling revealed that: Role stress had a direct positive effect on compassion fatigue; Perceived social support and emotional regulation efficacy partially mediated the link between role stress and compassion fatigue respectively; And there was a chain mediating role of perceived social support and emotional regulation efficacy between role stress and compassion fatigue. Conclusion: The incidence of compassion fatigue was high during the COVID-19 pandemic among bedside nurses in China. Improving social support and enhancing the efficacy of emotion regulation may help alleviate compassion fatigue directly and/or via buffering the impact of role stress.