Z-Scheme Ag2S-Ag-In2O3 Heterostructure with Efficient Antibiotics Removal under Natural Sunlight.

The widespread distribution of antibiotics in natural waters is a great threat to human health. Photocatalytic degradation is an environmentally friendly technology to remediate antibiotic-polluted waters, driven by endless solar energy. Herein, a Z-scheme Ag2S-Ag-In2O3 heterostructure photocatalyst is prepared to remove antibiotics under environmental conditions. Under natural sunlight (light intensity: ∼78 mW/cm2) irradiation, the optimal Ag2S-Ag-In2O3 (10-ASAIO) exhibits considerable performance for decomposing diverse antibiotics, including norfloxacin (NOR), tetracycline hydrochloride, sulfisoxazole, ciprofloxacin, chlortetracycline hydrochloride, and ofloxacin. The NOR photodegradation rate constant of 10-ASAIO reaches 0.025 min-1, which is 12.50, 5.00, and 6.25 times higher than that of In2O3 (0.002 min-1), Ag-In2O3 (0.005 min-1), and Ag2S-In2O3 (0.004 min-1), respectively. This performance of the 10-ASAIO photocatalyst for decomposing NOR under natural sunlight exceeds most of the previously reported photocatalysts under a xenon lamp. Particularly, due to the intermittency of natural sunlight, a light-emitting diode (LED) lamp (light intensity: 5.1 mW/cm2) is also used as a light source, and 72.20% of NOR can be degraded with irradiation for 12 h. The effects of many water characteristics (water bodies, coexisting inorganic anions, pH, and humic acid) on the degradation performance of 10-ASAIO have been investigated, which exhibits stable degradation efficiency in variable aquatic environments. A 10-ASAIO catalyst-coated frosted glass sheet is fabricated to settle the problem of recovery of powder photocatalysts, and the immobilized catalyst shows outstanding activity and stability to decompose NOR. The photocatalytic mechanism and pathway of degrading NOR over 10-ASAIO have also been systemically investigated and proposed. The ecotoxicity (phytotoxicity and biotoxicity) of the 10-ASAIO photocatalyst and treated NOR solution have been tested by their toxic effects on cabbage seeds and Staphylococcus aureus (S. aureus). This work provides a feasible photocatalytic system for environmental pollutant remediation under natural sunlight or an LED lamp.

Comparison of Intercostal Nerve Block and Serratus Anterior Plane Block for Perioperative Pain Management and Impact on Chronic Pain in Thoracoscopic Surgery: A Randomized Controlled Trial.

OBJECTIVES: This study compares the analgesic efficacy of Intercostal Nerve Block (ICNB) under direct thoracoscopic visualization and Serratus Anterior Plane Block (SAPB) with ultrasound guidance during thoracoscopic surgery's perioperative period. Furthermore, it examines their impact on chronic pain and identifies potential risk factors associated with its development. METHODS: In this prospective randomized controlled study, 74 thoracoscopic surgery patients were randomly assigned to ICNB or SAPB groups. Attending surgeons administered ICNB, while anesthesiologists performed SAPB, both using 20 mL of 0.5% ropivacaine. Primary outcomes included Visual Analog Scale (VAS) scores for resting and coughing pain at 6, 12, 24, and 48 hours postoperatively, perioperative opioid and NSAID consumption, and chronic pain incidence at 3 months postoperatively. Secondary outcomes aimed to identify independent risk factors for chronic pain. RESULTS: The primary results reveal that SAPB group exhibited significantly lower VAS scores than ICNB group for postoperative coughing at 24 hours (P<0.001, 95% CI=[0.5, 1]) and for resting pain at 48 hours (P=0.001, 95% CI=[0.2, 1]). Conversely, ICNB group demonstrated reduced VAS score for resting pain at 6 hours compared to SAPB group (P=0.014, 95% CI=[-0.5, 0.5]). SAPB group required significantly less intraoperative sulfentanil (P<0.001, 95% CI=[2.5, 5]), remifentanil (P=0.005, 95% CI=[-0.4, -0.1]), and flurbiprofen ester (P=0.003, 95% CI=[0, 50]) than ICNB group. Chronic pain incidence was similar (P=0.572, 95% CI=[0.412, 1.279]), with mild pain in both ICNB and SAPB groups. Secondary findings indicate that resting VAS score at 12 hours (OR=7.59, P=0.048, 95% CI=[1.02, 56.46]), chest tube duration (OR=3.35, P=0.029, 95% CI=[1.13, 9.97]), and surgical duration (OR=1.02, P=0.049, 95% CI=[1.00, 1.03]) were significant predictors of chronic pain occurrence. DISCUSSION: ICNB and SAPB demonstrated comparable analgesic effects, with similar rates of chronic pain occurrence. Chronic pain independent risk factors included resting VAS score at 12 hours, chest tube duration, and surgical duration.

Construction of living-cell tissue engineered amniotic membrane for ocular surface disease.

BACKGROUND: Human amniotic membrane (AM) transplantation has been applied to treat ocular surface diseases, including corneal trauma. The focus of much deliberation is to balance the mechanical strength of the amniotic membrane, its resistance to biodegradation, and its therapeutic efficacy. It is commonly observed that the crosslinked human decellularized amniotic membranes lose the functional human amniotic epithelial cells (hAECs), which play a key role in curing the injured tissues. METHODS AND RESULTS: In this study, we crosslinked human decellularized amniotic membranes (dAM) with genipin and re-planted the hAECs onto the genipin crosslinked AM. The properties of the AM were evaluated based on optical clarity, biodegradation, cytotoxicity, and ultrastructure. The crosslinked AM maintained its transparency. The color of crosslinked AM deepened with increasing concentrations of genipin. And the extracts from low concentrations of genipin crosslinked AM had no toxic effect on human corneal epithelial cells (HCECs), while high concentrations of genipin exhibited cytotoxicity. The microscopic observation and H&E staining revealed that 2 mg/mL genipin-crosslinked dAM (2 mg/mL cl-dAM) was more favorable for the attachment, migration, and proliferation of hAECs. Moreover, the results of the CCK-8 assay and the transwell assay further indicated that the living hAECs' tissue-engineered amniotic membranes could facilitate the proliferation and migration of human corneal stromal cells (HCSCs) in vitro. CONCLUSIONS: In conclusion, the cl-dAM with living hAECs demonstrates superior biostability and holds significant promise as a material for ocular surface tissue repair in clinical applications.

Bimetallic Au/Ag coated on In2O3 for the effective removal of emerging organic contaminants under natural sunlight irradiation.

Antibiotics-polluted wastewater, likely causing the spread of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs), can be effectively remediated by photocatalytic degradation driven by endless solar energy. Herein, bimetallic Au/Ag is deposited on In2O3 surface via a one-step sintering process followed by a controllable chemical reduction approach. Under natural sunlight irradiation, the optimal Au/Ag/In2O3 (UGI-1.0) photocatalyst possesses a considerable norfloxacin (NOR) degradation rate constant of 0.013 min-1, which is 3.25, 1.63, and 1.86 times higher than that of In2O3, Ag/In2O3, and Au/In2O3 respectively. The effect of many water characteristics (e.g., humic acid, water bodies, pH values, and coexisting anions) on the photodegradation performance of NOR over UGI-1.0 is investigated. Moreover, other persistent organic pollutants (ofloxacin, phenol, 2,4-dichlorophenol, and rhodamine B) can also be degraded over UGI-1.0, suggesting its universal oxidation capacity. To settle the challenge of powder photocatalyst recovery, the UGI-1.0 photocatalyst is coated on a frosted glass sheet, which exhibits outstanding activity and stability for degrading NOR. The bimetallic Au/Ag deposited on In2O3 promote its photo-absorption, and enhance its photoinduced charge separation and transfer efficiency by serving as electron accepter, leading to the boosted activity of Au/Ag/In2O3 catalysts. Particularly, the cultivation of staphylococcus aureus (S. aureus) and cabbage seeds reveals the efficient toxicity reduction of NOR by photocatalytic degradation and the nontoxic characteristic of UGI-1.0 catalyst. This work unveils the feasibility of UGI-1.0 to remediate real wastewater with the assistance of solar energy.

Characterization of the flavor profile and dynamic changes in Chinese traditional fish sauce (Yu-lu) based on electronic nose, SPME-GC-MS and HS-GC-IMS.

In this study, flavor characteristics and dynamic change of Chinese traditional fermented fish sauce (Yu-lu) with different fermentation time (2, 4, 6, 8, and 12 months) were analyzed. The electronic nose analyses confirmed a notable flavor change in fish sauce samples from different stages. During the 12-months fermentation, the total volatile compounds in fish sauce increased from 3.9 mg/L to 13.53 mg/L. Acids, aldehydes, esters and phenols were the main aroma substances and their contents gradually increased during the fermentation process. The PCA of GC-MS and GC-IMS showed that fish sauce samples from different fermentation periods can be well distinguished. A total of 110 volatile compounds identified by GC-MS, and 102 volatile compounds were detected by GC-IMS. Among them, 13 compounds were identified by both GC-MS and GC-IMS. The most varieties (49) of volatiles appeared after 8 months of fermentation. The odor activity value (OAV) analysis showed that 10 volatile compounds were considered as characteristic flavor in traditional fish sauce. The variable influence on projections (VIPs) in PLS-DA models constructed by GC-MS and GC-IMS identified 5 and 10 volatile compounds as biomarkers, respectively. Our results revealed the dynamic changes of characteristic flavor in fish sauce in combination of GC-MS and GC-IMS, which provides theoretical basis for the production and flavor regulation of fish sauce.

Elucidating Microglial Heterogeneity and Functions in Alzheimer's Disease Using Single-cell Analysis and Convolutional Neural Network Disease Model Construction.

In this study, we conducted an in-depth exploration of Alzheimer's Disease (AD) by integrating state-of-the-art methodologies, including single-cell RNA sequencing (scRNA-seq), weighted gene co-expression network analysis (WGCNA), and a convolutional neural network (CNN) model. Focusing on the pivotal role of microglia in AD pathology, our analysis revealed 11 distinct microglial subclusters, with 4 exhibiting obviously alterations in AD and HC groups. The investigation of cell-cell communication networks unveiled intricate interactions between AD-related microglia and various cell types within the central nervous system (CNS). Integration of WGCNA and scRNA-seq facilitated the identification of critical genes associated with AD-related microglia, providing insights into their involvement in processes such as peptide chain elongation, synapse-related functions, and cell adhesion. The identification of 9 hub genes, including USP3, through the least absolute shrinkage and selection operator (LASSO) and COX regression analyses, presents potential therapeutic targets. Furthermore, the development of a CNN-based model showcases the application of deep learning in enhancing diagnostic accuracy for AD. Overall, our findings significantly contribute to unraveling the molecular intricacies of microglial responses in AD, offering promising avenues for targeted therapeutic interventions and improved diagnostic precision.

Targeting the sulfur-containing amino acid pathway in leukemia.

sulfur-containing amino acids have been reported to patriciate in gene regulation, DNA methylation, protein synthesis and other physiological or pathological processes. In recent years, metabolism-related molecules of sulfur-containing amino acids affecting the occurrence, development and treatment of tumors have been implicated in various disorders, especially in leukemia. Here, we summarize current knowledge on the sulfur-containing amino acid metabolism pathway in leukemia and examine ongoing efforts to target this pathway, including treatment strategies targeting (a) sulfur-containing amino acids, (b) metabolites of sulfur-containing amino acids, and (c) enzymes and cofactors related to sulfur-containing amino acid metabolism in leukemia. Future leukemia therapy will likely involve innovative strategies targeting the sulfur-containing amino acid metabolism pathway.

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 1 year. Patients' clinical data were collected. The levels of BTMs 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 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 decreased 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.

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.

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.

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.

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.

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.

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.