Changes in serum bone turnover markers and bone mineral density Z-score in children with osteogenesis imperfecta after zoledronic acid treatment.

The study aimed to investigate the changes in the levels of serum bone turnover markers (BTMs) and bone mineral density (BMD) Z-score in pediatric patients with osteogenesis imperfecta (OI) after intravenous bisphosphonate therapy, and their association with age and estimated glomerular filtration rate (eGFR).This retrospective study analyzed data from 10 pediatric OI patients treated with intravenous zoledronic acid for over one year. Patients' clinical data were collected. The levels of bone turnover markers, and BMD Z-score before and after zoledronic acid treatment were analyzed. Significant improvement in BMD Z-score was observed after 6 and 12 months of treatment compared to baseline (all p < 0.05). The N-terminal propeptide of type I procollagen (PINP) levels decreased over time (all p < 0.05), indicating that zoledronic acid treatment decreased bone turnover. The levels of beta-C-terminal telopeptide of type I collagen (ß-CTX) remained stable after treatment. No correlation was found between PINP level and age, eGFR, or BMD (all p > 0.05). Bisphosphonate treatment can improve BMD and decrease bone turnover (indicated by decrease levels of PINP) in pediatric OI patients. PINP may serve as an independent indicator for monitoring the efficacy of bisphosphonate treatment in pediatric OI patients, particularly in those under the age of 6, where standardized BMD Z-score criteria are lacking.

Meta-analysis of the correlation between pulmonary hypertension and echocardiographic parameters in patients with chronic kidney disease.

Objective: To investigate the correlation between pulmonary hypertension (PH) and echocardiographic parameters in patients with chronic kidney disease (CKD). Methods: PubMed, Embase, Web of Science, Cochrane, VIP, CNKI, and Wanfang databases were systematically searched for articles published from inception to 19 May 2023. Study quality was estimated using the Quality Assessment of Case-Control Studies tool. Forest plots were drawn using R language software. The "metacor" function in the "meta" package was utilized for meta-analysis of the r-values and their standard errors. Heterogeneity and sensitivity analyses were carried out, with the main outcomes as r-value, p-value, and I2 value. Results: Eleven studies were included, with 1,809 CKD patients. The correlations between 12 echocardiographic parameters and PH were analyzed. Except for FS and LVEF which were negatively correlated with CKD-PH, the other 10 parameters were positively correlated with CKD-PH. Among them, LA was highly correlated with CKD-PH (0.70 < r < 0.89); LVDD, RA, RV, LVMI, and LVDS were moderately correlated with CKD-PH (0.40 < r < 0.69); while PA, IVS, LVPW, SV, FS, and LVEF were lowly correlated with CKD-PH (0.20 < r < 0.39). The synthesized estimates were stable against heterogeneity. Conclusion: CKD-PH patients may have large cardiac chambers, thickened septal tissue on both sides of the chambers, reduced pulmonary artery flow rates, and decreased left ventricular function.

Boosting the activity for organic pollutants removal of In2O3 by loading Ag particles under natural sunlight irradiation.

A novel photocatalyst In2O3 with loading Ag particles is prepared via a facile one-step annealing method in air atmosphere. The Ag/In2O3 exhibits considerable photoactivity for decomposing sulfisoxazole (SOX), tetracycline hydrochloride (TC), and rhodamine B (RhB) under natural sunlight irradiation, which is much higher than that of pristine In2O3 and Ag species. After natural sunlight irradiation for 100 min, 70.6% of SOX, 65.6% of TC, and 81.9% of RhB are degraded over Ag/In2O3, and their corresponding chemical oxygen demand (COD) removal ratio achieve 95.4%, 38.4%, and 93.6%, respectively. A batch of experiments for degrading SOX with adjusting pollutant solution pH and adding coexisting anions over Ag/In2O3 are carried out to estimate its practical application prospect. Particularly, the as-prepared Ag/In2O3 possesses a superior stability, which exhibits no noticeable deactivation in decomposing SOX after eight cycles' reactions. In addition, the Ag/In2O3 coated on a frosted glass plate, also possesses a superior activity and stability for SOX removal, which solve the possible second pollution of residual powdered catalyst in water. Ag particles on In2O3 working as electron accepter improve charge separation and transfer efficiency, as well as the photo-absorption and organic pollutants affinity, leading to the boosted photoactivity of Ag/In2O3. The photocatalytic mechanism for degrading SOX and degradation process over Ag/In2O3 has been systemically investigated and proposed. This work offers an archetype for the rational design of highly efficient photocatalysts by metal loading.

Photocatalytic Three-Component Reaction for the Synthesis of Multifunctional Diaryl Sulfides.

A photocatalytic three-component reaction of a nitroarene, a thiophenol, and a ketone for the synthesis of multifunctional diaryl sulfides was reported using a nitro group as the nitrogen source and thiophenol as the sulfur source. Thiophenol also serves as a proton donor to reduce nitroarene to arylamine as a key intermediate for the formation of C-N and C-S bonds. Good functional group tolerance and mild reaction conditions make this method have practical synthetic value for diversified multifunctional diaryl sulfides.

Gender-Based Differential Item Function for the Positive and Negative Semantic Dimensions of the Relationship Satisfaction Scale with Item Response Theory.

Relationship satisfaction is at the core of a robust social life and is essential to mental health. The positive and negative semantic dimensions of the relationship satisfaction (PN-SMD) scale is considered in the field of relationship studies to be a reliable tool for assessing the quality of a person's interpersonal relationships. This study evaluated the psychometric properties of the PN-SMD scale by conducting multidimensional item response theory (MIRT) and differential item functioning (DIF) analyses, both of which are emerging assessment methods that focus on individual items. We recruited 511 Chinese undergraduate students for this study. Construct validity, internal consistency, and concurrent validity were assessed, and MIRT and DIF analyses were conducted. Five of the 14 items were found to have gender-based DIF traits, affecting the scale's construct validity. A revised nine-item scale (DIF items excluded) had a significantly better model fit and demonstrated comparable concurrent validity to the original scale. The implications of our results and future research directions are discussed.

Clinical heterogeneity and therapeutic options for idiopathic infantile hypercalcemia caused by CYP24A1 pathogenic variant.

OBJECTIVES: Infantile hypercalcemia-1 (HCINF1) is a rare disease caused by pathogenic variants in the CYP24A1 gene, resulting in the inability to metabolize active vitamin D. This leads to hypercalcemia and severe complications. CONTENT: On December 8th, 2022, a systematic literature search was conducted in PubMed, Wanfang, and CNKI using the keywords "hypercalcemia" and "CYP24A1". Data extraction included patient demographics, clinical presentation, treatment medications, and outcomes. The findings were synthesized to identify common patterns and variations among cases and to assess the efficacy of different therapies in reducing serum calcium. Our findings revealed two distinct peaks in the incidence of HCINF1 caused by CYP24A1 pathogenic variant. Kidney stones or renal calcifications were the most common clinical manifestations of the disease, followed by polyuria and developmental delay. Laboratory investigations showed hypercalcemia, elevated vitamin D levels, hypercalciuria, and low parathyroid hormone. Genetic analysis remains the only reliable diagnostic tool. Although there is no definitive cure for HCINF1, multiple drugs, including bisphosphonates, calcitonin, and rifampicin, have been used to control its symptoms. Blocking the production and intake of vitamin D is the preferred treatment option. SUMMARY AND OUTLOOK: Our review highlights the basic clinical and biochemical features of HCINF1 and suggests that targeted diagnostic and therapeutic strategies are needed to address the clinical heterogeneity of the disease. The insights gained from this study may facilitate the development of innovative treatments for HCINF1.

Visible-Light-Mediated Three-Component Decarboxylative Coupling Reactions to Synthesize 1,4-Diol Monoethers.

An efficient approach for 1,2-difunctionalization of aromatic olefins and the synthesis of functionalized 1,4-diols monoethers has been established via a photoinduced three-component reaction of an α-alkoxycarboxylic acid, an aromatic olefin, and an aldehyde. The reaction proceeds by photoinduced oxidative decarboxylation of the carboxylic acid followed by the addition of the α-alkoxyalkyl radical to the olefin, one-electron reduction of the addition radical, and the nucleophilic attack of the resulting carbanion to the aldehyde. Besides the convenient one-pot protocol of the three-component reaction, this method offers several other advantages, including good functional group tolerance for the three substrates, gentle reaction conditions, and ease of scaling up. The reaction mechanism has been investigated through free radical trapping experiment and isotope labeling experiments.

The potential of white-rot fungi for algal control: Mechanisms, Strategies, and Challenges.

As human society and industrialization have progressed, harmful algal blooms have contributed to global ecological pollution which makes the development of a novel and effective algal control strategy imminent. This is because existing physical and chemical methods for dealing with the problem have issues like cost and secondary pollution. Benefiting from their environmentally friendly and biocompatible properties, white-rot fungi (WRF) have been studied to control algal growth. WRF control algae by using algae for carbon or nitrogen, antagonism, and enhancing allelopathies. It can be better applied to practice by immobilization. This paper reviews the mechanism for WRF control of algae growth and its practical application. It demonstrates the limitations of WRF controlling algae growth and aids the further study of biological methods to regulate eutrophic water in algae growth research. In addition, it provides theoretical support for the fungi controlling algae growth.

Successful treatment of hypercalcemia in a Chinese patient with a novel homozygous mutation in the CYP24A1 gene using zoledronic acid: a case report.

OBJECTIVES: To emphasize the significance of genetic mutations in idiopathic infantile hypercalcemia and the potential therapeutic effectiveness of zoledronic acid in managing hypercalcemia attributed to gene mutations. CASE PRESENTATION: A 1-year-old female infant was referred to our hospital. The patient developed hypercalcemia despite no vitamin D prophylaxis or intake. In the acute phase, conventional calcium-lowering treatments showed limited efficacy, while the administration of zoledronic acid demonstrated effectiveness in controlling hypercalcemia. Subsequently the patient maintained normal calcium levels via a low-calcium diet and avoiding vitamin D intake. Genetic testing confirmed a homozygous mutation (c.476G>C) in the CYP24A1 gene. CONCLUSIONS: Family screening and genetic counseling are crucial for early detection and prevention of hypercalcemia. This case emphasizes the importance of genetic mutations in disease development and the potential therapeutic efficacy of zoledronic acid in managing hypercalcemia attributed to gene mutations.

Targeting transient receptor potential canonical 1 reduces non­small cell lung cancer chemoresistance and stemness via inhibition of PI3K/AKT signaling.

TRPC1 enhances cell proliferation and migration in non-small cell lung cancer (NSCLC); however, its effect on NSCLC chemoresistance and stemness remains to be determined. The aim of the current study was to investigate the effect of TRPC1 on NSCLC chemoresistance and stemness and to determine the underlying mechanism of action. Cisplatin-resistant A549 (A549/CDDP) and H460 (H460/CDDP) cells were first established and were then transfected with negative control small interfering (si)RNA (si-NC) or TRPC1 siRNA (si-TRPC1). Cells were then treated with 740 Y-P, a PI3K/Akt agonist. Subsequently, the sensitivity of A549/CDDP and H460/CDDP cells to CDDP was evaluated. Furthermore, the expression levels of CD133 and CD44, and sphere formation ability were also determined. The results showed that the half-maximal inhibitory concentration (IC50) of CDDP was significantly higher in A549/CDDP cells compared with A549 cells and in H460/CDDP cells compared with H460 cells. TRPC1 silencing decreased the IC50 value of CDDP compared with the si-NC group in A549/CDDP (11.78 vs. 21.58 µM; P<0.01) and H460/CDDP (23.76 vs. 43.11 µM; P<0.05) cells. Additionally, TRPC1 knockdown in both cell lines decreased the number of spheres formed compared with the si-NC group. Furthermore, compared with the si-NC group, A549/CDDP cells transfected with si-TRPC1 exhibited decreased levels of both CD133 (P<0.01) and CD44 (P<0.05). However, only CD133 (P<0.05) was downregulated in TRPC1-depleted H460/CDDP cells compared with the si-NC group. In addition, TRPC1 knockdown repressed PI3K/AKT signaling compared with the si-NC group in both A549/CDDP and H460/CDDP cells (all P<0.05). Finally, cell treatment with 740 Y-P reversed the effect of TRPC1 knockdown on PI3K/AKT signaling, chemoresistance, and cancer stemness in A549/CDDP and H460/CDDP cells (all P<0.05). In conclusion, the results of the current study suggested that targeting TRPC1 could attenuate cancer stemness and chemoresistance via suppression of PI3K/AKT signaling in NSCLC.

Suppression of NLRP3/Caspase-1/GSDMD Mediated Corneal Epithelium Pyroptosis Using Melatonin-Loaded Liposomes to Inhibit Benzalkonium Chloride-Induced Dry Eye Disease.

Introduction: Benzalkonium chloride (BAC) is widely employed as a preservative in eye drops, which will cause the death of corneal epithelial cells due to ROS production, DNA strand breakage, and mitochondrial dysfunction, resulting in dry eye disease (DED)-like changes in ocular surface tissues. In this study, Melatonin (MT) liposomes (TAT-MT-LIPs) designed by loading MT into TAT-modified liposomes have been developed, characterized, and used for inhibiting BAC-induced DED (BAC-DED). Methods: The TAT was chemically grafted onto the Mal-PEG2000-DSPE by Michael's addition between the sulfhydryl group in TAT and the maleimide group in Mal-PEG2000-DSPE. TAT-MT-LIPs were prepared using film dispersion followed by the extrusion method and topically treated in rats once a day. BAC-DED was induced in rats by topical administration with 0.2% BAC twice daily. Defects, edema, and inflammation of the corneas, as well as IOP, were examined. Histologic analyses of corneas were performed to assess the change of mitochondrial DNA oxidation and NLRP3/Caspase-1/GSDMD signaling transduction. Results: After topical administration, TAT-MT-LIPs significantly alleviated DED-clinical symptoms of experimental animals by inhibiting tissue inflammation and preventing the loss of the corneal epithelium and conjunctival goblet cells. Our data suggested continuous ocular surface exposure of BAC-induced NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis, which was not reported before. BAC caused substantial mt-DNA oxidation, which promoted the transduction of NLRP3/Caspase-1/GSDMD and consequent corneal epithelium pyroptosis. TAT-MT-LIPs could efficiently suppress the BAC-induced corneal epithelium pyroptosis and inflammation by inhibiting mt-DNA oxidation and the subsequent signal transmission. Conclusion: NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis is involved in the development of BAC-DED. The present study provided new insights into the adverse effects of BAC, which can serve as a new target for protecting corneal epithelium when applying BAC as a preservative in eye drops. The developed TAT-MT-LIPs can efficiently inhibit BAC-DED and give great potential to be developed as a new DED treatment.

Efficiency Encapsulation of FK506 with New Dual Self-Assembly Multi-Hydrophobic-Core Nanoparticles for Preventing Keratoplasty Rejection.

Nanoparticles self-assembled by amphiphilic copolymers for loading hydrophobic molecules are intensively investigated. However, their hydrophobic molecule-loading capacity is low due to the limitation of hydrophobic groups in these copolymers. In this regard, new lysine oligomer-based multi-hydrophobic side chain polymers (MHCPs) are synthesized by polymerization of γ-benzyl-l glutamate N-carboxy anhydride initiated by side-chain primary amino groups in lysine oligomer. Each hydrophobic side chain in MHCPs can be self-assembled by hydrophobic interaction to form multi-hydrophobic-core nanoparticles (MHC-NPs) with silkworm cocoon-, grape cluster-, and butterfly-like shapes (depending on hydrophobic-side-chains lengths). To increase their stability, MHC-NPs are dually self-assembled with polyethylene glycol-polyglutamic acid through charge interaction. Each hydrophobic core in MHC-NPs serves as a carrier for hydrophobic molecules, endowing their nanostructure with high loading capacity. MHC-NPs are employed to load tacrolimus (also known as FK506), and the loading amount is 18% and the loading efficiency is 80%, which are higher than those of previously reported nanomicelles self-assembled by linear amphiphilic copolymers. Topical administration of FK506-loaded nanoparticle (FK506-NP) can significantly prolong retention of FK506 on the eye surface. FK506-NP exhibits higher in vivo immunosuppressive effects than free FK506 and commercial FK506 eye drop, as well as a better protective effect against immunotoxicity in the corneal grafts after keratoplasty.

Bioinformatics-integrated screening of systemic sclerosis-specific expressed markers to identify therapeutic targets.

Background: Systemic sclerosis (SSc) is a rare autoimmune disease characterized by extensive skin fibrosis. There are no effective treatments due to the severity, multiorgan presentation, and variable outcomes of the disease. Here, integrated bioinformatics was employed to discover tissue-specific expressed hub genes associated with SSc, determine potential competing endogenous RNAs (ceRNA) regulatory networks, and identify potential targeted drugs. Methods: In this study, four datasets of SSc were acquired. To identify the genes specific to tissues or organs, the BioGPS web database was used. For differentially expressed genes (DEGs), functional and enrichment analyses were carried out, and hub genes were screened and shown in a network of protein-protein interactions (PPI). The potential lncRNA-miRNA-mRNA ceRNA network was constructed using the online databases. The specifically expressed hub genes and ceRNA network were validated in the SSc mouse and in normal mice. We also used the receiver operating characteristic (ROC) curve to determine the diagnostic values of effective biomarkers in SSc. Finally, the Drug-Gene Interaction Database (DGIdb) identified specific medicines linked to hub genes. Results: The pooled datasets identified a total of 254 DEGs. The tissue/organ-specifically expressed genes involved in this analysis are commonly found in the hematologic/immune system and bone/muscle tissue. The enrichment analysis of DEGs revealed the significant terms such as regulation of actin cytoskeleton, immune-related processes, the VEGF signaling pathway, and metabolism. Cytoscape identified six gene cluster modules and 23 hub genes. And 4 hub genes were identified, including Serpine1, CCL2, IL6, and ISG15. Consistently, the expression of Serpine1, CCL2, IL6, and ISG15 was significantly higher in the SSc mouse model than in normal mice. Eventually, we found that MALAT1-miR-206-CCL2, let-7a-5p-IL6, and miR-196a-5p-SERPINE1 may be promising RNA regulatory pathways in SSc. Besides, ten potential therapeutic drugs associated with the hub gene were identified. Conclusions: This study revealed tissue-specific expressed genes, SERPINE1, CCL2, IL6, and ISG15, as effective biomarkers and provided new insight into the mechanisms of SSc. Potential RNA regulatory pathways, including MALAT1-miR-206-CCL2, let-7a-5p-IL6, and miR-196a-5p-SERPINE1, contribute to our knowledge of SSc. Furthermore, the analysis of drug-hub gene interactions predicted TIPLASININ, CARLUMAB and BINDARIT as candidate drugs for SSc.

[Effect of electroacupuncture on transforming growth factor-ß1 and renal tubular epithelial mesenchymal transformation in renal tissue of spontaneously hypertensive rats].

OBJECTIVE: To observe the effects of electroacupuncture (EA) on renal fibrosis, the expression of transforming growth factor-ß1 (TGF-ß1) and epithelial mesenchymal transition (EMT) marker proteins in renal tissue of spontaneously hypertensive rats (SHR), so as to explore the underlying mechanism on EA alleviating hypertensive renal impairment. METHODS: Twenty-four male SHR were randomly divided into model group, losartan group and EA group, with 8 rats in each group, and eight male Wistar-Kyoto rats were taken as the normal group. Rats in the losartan group received gavage of losartan potassium solution (3 mg/mL, 30 mg·kg-1·d-1),once every other day for 12 weeks. Rats in the EA group received EA stimulation at bilateral "Shenshu" (BL23) and "Geshu" (BL17) (2 Hz/15 Hz, 1.0 mA), 15 min each time, once every other day for 12 weeks. The systolic blood pressure of caudal artery was measured before, and 4, 8 and 12 weeks after the intervention. The 24-hour urinary protein was measured before, and 6 and 12 weeks after the intervention. Histopathological changes of the left renal tissue were observed under light mircoscope after H.E. stain. Extracellular matrix (ECM) in renal tissues was observed after periodate Schiff staining. Basement membrane and collagen fibers were observed after Masson staining with collagen volume fraction (CVF) evaluated. The expression of TGF-ß1 mRNA in the right renal was detected by real-time fluorescence quantitative PCR. The expression of TGF-ß1 and EMT marker E-cadherin, α-SMA and fibronectin (FN) proteins in the left renal tissue was measured by immunohistochemistry. RESULTS: In the model group, irregular arrangement of nephrocytes, renal tubule atrophy, lumen stenosis, ECM hyperplasia and deposition, scar and sclerosis were observed, which were relatively milder in the EA and losartan groups. Compared with the normal group, tubulointerstitium CVF, systolic blood pressure of caudal artery before, and at 4, 8 and 12 weeks after the intervention, 24-hour urinary protein before, and at 6 and 12 weeks after the intervention, the expression of TGF-ß1 mRNA, area of TGF-ß1, α-SMA and FN positive staining in renal tissues were significantly increased (P<0.01), while the area of E-cadherin positive staining was significantly decreased (P<0.01) in the model group. Compared with the model group, tubulointerstitium CVF, systolic blood pressure of caudal artery at 4, 8 and 12 weeks after the intervention, 24-hour urinary protein at 6 and 12 weeks after the intervention, the expression of TGF-ß1 mRNA, area of TGF-ß1, α-SMA and FN positive staining in renal tissues were significantly decreased (P<0.01，P<0.05), while area of E-cadherin positive staining was significantly increased (P<0.01) in the losartan and EA groups. Compared with the losartan group, the area of E-cadherin was conside-rately increased (P<0.01), while the area of α-SMA protein decreased (P<0.01) in the EA group. CONCLUSION: EA could effectively alleviate hypertension and renal interstitial fibrosis in SHR, the mechanism of which may be related to its function in reducing the expression of TGF-ß1 and inhibiting EMT in renal tissue.

Predictors and moderators of COVID-19 pandemic fatigue in Hong Kong.

BACKGROUND: Anti-pandemic fatigue has inevitably set in owing to the high intensity and prolonged presence of pandemic preventive measures. Globally, COVID-19 remains severe; however, pandemic fatigue may lead to less efficient viral control. METHODS: A total of 803 participants residing in Hong Kong interviewed via telephone using a structured questionnaire. Linear regression was employed to test the corelates of anti-pandemic fatigue and the moderators that could potentially impact the appearance of fatigue. RESULTS: When confounding effects of demographic factors (e.g., age, gender, educational attainment, and economic activity status) were avoided, daily hassles were found to be a core factor associated with anti-pandemic fatigue (B =0.369, SE =0.049, p = 0.000). For people with a higher level of pandemic-related knowledge and fewer obstacles brought about by preventive measures, the impact of daily hassles on pandemic fatigue weakened. Moreover, when pandemic-related knowledge was high, there was no positive association between adherence and fatigue. CONCLUSIONS: This study confirms that daily hassles can lead to anti-pandemic fatigue, which can be mitigated by improving the general public's understanding of the virus and developing more convenient measures.

Advances in the Application of the Non-Conventional Yeast Pichia kudriavzevii in Food and Biotechnology Industries.

Pichia kudriavzevii is an emerging non-conventional yeast which has attracted increased attention for its application in food and biotechnology areas. It is widespread in various habitats and often occurs in the spontaneous fermentation process of traditional fermented foods and beverages. The contributions of P. kudriavzevii in degrading organic acid, releasing various hydrolase and flavor compounds, and displaying probiotic properties make it a promising starter culture in the food and feed industry. Moreover, its inherent characteristics, including high tolerance to extreme pH, high temperature, hyperosmotic stress and fermentation inhibitors, allow it the potential to address technical challenges in industrial applications. With the development of advanced genetic engineering tools and system biology techniques, P. kudriavzevii is becoming one of the most promising non-conventional yeasts. This paper systematically reviews the recent progress in the application of P. kudriavzevii to food fermentation, the feed industry, chemical biosynthesis, biocontrol and environmental engineering. In addition, safety issues and current challenges to its use are discussed.

Visible-light induced three-component reaction for α-aminobutyronitrile synthesis by C-C bond formation using quantum dots as photocatalysts.

We describe a three-component reaction of malononitrile, benzaldehyde and N,N-dimethylaniline using aluminium doped CdSeS/CdZnSeS(Al)/ZnS quantum dots (QDs) as visible light catalysts to synthesize α-aminobutyrilitriles at room temperature and under mild conditions. The reactions exhibit high functional group tolerance, and the well dispersed quantum dot catalysts are highly efficient with a turnover number (TON) greater than 1.1 × 103 and can be recycled at least three times without significant loss of catalytic activity.

Comparison of EGFR mutations detected by LNA-ARMS PCR in plasma ctDNA samples and matched tissue sample in non-small cell lung cancer patients.

BACKGROUND: Screening for epidermal growth factor receptor (EGFR) mutations is the key to select suitable patients with non-small cell lung cancer (NSCLC) for EGFR-TKI therapy in clinical practice. Nevertheless, tumor tissue that needed for mutation analysis is frequently unavailable, especially for patients with recurrence after operation. Therefore, detection of EGFR from circulating tumor DNA (ctDNA) in patients with NSCLC is a sensitive and convenient method to direct patient sequential treatment strategy. METHODS: One hundred and seventy-nine NSCLC patients with both tumor tissue samples and paired plasma samples were recruited. EGFR mutations were detected in 68 tumor tissue samples and 179 plasma samples using Anlongen Locked Nucleic Acid-Amplification Refractory Mutation System (LNA-ARMS) EGFR Mutation Detection Kit. The remaining 111 tumor tissue samples were detected with the use of multiplex PCR-Based NGS sequence. We calculated the sensitivity, specificity, positive prediction value (PPV) and negative prediction value (NPV) of LAN-ARMS PCR. The objective response rate (ORR) of patients received TKIs therapy was calculated. RESULTS: Of the 179 patients, EGFR mutations were detected in 77 of the 179 tumor tissue samples, with a positive rate of 43.01% (77/179). In addition, EGFR mutations were detected in 42 of the 179 plasma samples. The sensitivity and specificity of LAN-ARMS in detecting EGFR mutations were 57.18% and 98.04% respectively compared to tissue results. The PPV was 95.24%, and NPV was 72.99%. Of the 179 pair of samples, EGFR mutations were inconsistent in 39 pairs of tissue and plasma. The overall agreement of EGFR mutation detection was 78.21% (140/179). The ORR was higher in patients with both tissue and plasma EGFR mutations compared with that in patients with only tissue EGFR mutations (73.33% vs. 68.29%), but the difference was not significant. It was suggested that tissue detection combined with plasma detection could improve the mutation rate. CONCLUSION: In plasma samples, Anlongen LAN-ARMS EGFR Mutation Detection Kit had a high sensitivity and specificity for the detection of EGFR mutations. Anlongen LAN-ARMS EGFR Mutation Detection Kit had the advantages of easy-to-operate and high sensitivity in clinical application.

Human amniotic epithelial cell-derived extracellular vesicles provide an extracellular matrix-based microenvironment for corneal injury repair.

To study the biological functions and applications of human amniotic epithelial cell-derived extracellular vesicles (hAEC-EVs), the cargos of hAEC-EVs were analyzed using miRNA sequencing and proteomics analysis. The hAECs and hAEC-EVs in this study had specific characteristics. Multi-omics analyses showed that extracellular matrix (ECM) reorganization, inhibition of excessive myofibroblasts, and promotion of target cell adhesion to the ECM were their primary functions. We evaluated the application of hAEC-EVs for corneal alkali burn healing in rabbits and elucidated the fundamental mechanisms. Slit-lamp images revealed that corneal alkali burns induced central epithelial loss, stromal haze, iris, and pupil obscurity in rabbits. Slit-lamp examination and histological findings indicated that hAEC-EVs facilitated re-epithelialization of the cornea after alkali burns, reduced scar formation and promoted the restoration of corneal tissue transparency. Significantly fewer α-SMA-positive myofibroblasts were observed in the hAEC-EV-treated group than the PBS group. HAEC-EVs effectively promoted the proliferation and migration of hCECs and hCSCs in vitro and activated the focal adhesion signaling pathway. We demonstrated that hAEC-EVs were excellent cell-free candidates for the treatment of ECM lesion-based diseases, including corneal alkali burns. HAEC-EVs promoted ECM reorganization and cell adhesion of target tissues or cells via orderly activation of the focal adhesion signaling pathway.

miR­363­3p attenuates the oxygen­glucose deprivation/reoxygenation­induced neuronal injury in vitro by targeting PDCD6IP.

The purpose of the present study was to explore the functional role of microRNA (miR)­363­3p and related regulatory mechanisms in cerebral ischemia/reperfusion (I/R) injury. The neuronal cell line SH­SY5Y was exposed to 4 h of oxygen and glucose deprivation (OGD), followed by 6, 12, 24 and 48 h of re­oxygenation to mimic I/R injury in vitro. Cell viability, apoptosis and inflammation were assessed by CCK­8, lactate dehydrogenase (LDH), flow cytometry and ELISA assays. The association between miR­363­3p and programmed cell death 6­interacting protein (PDCD6IP) was further confirmed using luciferase reporter assay. Our data revealed that the expression level of miR­363­3p was significantly downregulated after OGD/R induction. Overexpression of miR­363­3p markedly suppressed OGD/R­induced cell injury, as reflected by attenuated cell viability, reduced apoptosis, LDH activity and pro­inflammatory cytokine levels. Mechanistically, PDCD6IP was confirmed as the target of miR­363­3p. Furthermore, PDCD6IP knockdown imitated, while overexpression reversed the effects of miR­363­3p overexpression on OGD/R­induced cell injury. Collectively, miR­363­3p could attenuate OGD/R­induced cell injury by alleviating apoptosis and inflammation, which may be mediated, at least in part, via inhibition of PDCD6IP.