M6A-mediated upregulation of lncRNA TUG1 in liver cancer cells regulates the antitumor response of CD8+ T cells and phagocytosis of macrophages.

Tumor immune evasion relies on the crosstalk between tumor cells and adaptive/innate immune cells. Immune checkpoints play critical roles in the crosstalk, and immune checkpoint inhibitors have achieved promising clinical effects. The long non-coding RNA taurine-upregulated gene 1 (TUG1) is upregulated in hepatocellular carcinoma (HCC). However, how TUG1 is upregulated and the effects on tumor immune evasion are incompletely understood. Here, METTL3-mediated m6A modification led to TUG1 upregulation is demonstrated. Knockdown of TUG1 inhibited tumor growth and metastasis, increased the infiltration of CD8+ T cells and M1-like macrophages in tumors, promoted the activation of CD8+ T cells through PD-L1, and improved the phagocytosis of macrophages through CD47. Mechanistically, TUG1 regulated PD-L1 and CD47 expressions by acting as a sponge of miR-141 and miR-340, respectively. Meanwhile, TUG1 interacted with YBX1 to facilitate the upregulation of PD-L1 and CD47 transcriptionally, which ultimately regulated tumor immune evasion. Clinically, TUG1 positively correlated with PD-L1 and CD47 in HCC tissues. Moreover, the combination of Tug1-siRNA therapy with a Pdl1 antibody effectively suppressed tumor growth. Therefore, the mechanism of TUG1 in regulating tumor immune evasion is revealed and can inform existing strategies targeting TUG1 for enhancing HCC immune therapy and drug development.

An 18-gene signature of recurrence-associated endothelial cells predicts tumor progression and castration resistance in prostate cancer.

BACKGROUND: The prognostic and therapeutic implications of endothelial cells (ECs) heterogeneity in prostate cancer (PCa) are poorly understood. METHODS: We investigated associations of EC heterogeneity with PCa recurrence and castration resistance in 8 bulk transcriptomic and 4 single-cell RNA-seq cohorts. A recurrence-associated EC (RAEC) signature was constructed by comparing 11 machine learning algorithms through nested cross-validation. Functional relevances of RAEC-specific genes were also tested. RESULTS: A subset of ECs was significantly associated with recurrence in primary PCa and named RAECs. RAECs were characteristic of tip and immature cells and were enriched in migration, angiogenesis, and collagen-related pathways. We then developed an 18-gene RAEC signature (RAECsig) representative of RAECs. Higher RAECsig scores independently predicted tumor recurrence and performed better or comparably compared to clinicopathological factors and commercial gene signatures in multiple PCa cohorts. Of the 18 RAECsig genes, FSCN1 was upregulated in ECs from PCa with higher Gleason scores; and the silencing of FSCN1, TMEME255B, or GABRD in ECs either attenuated tube formation or inhibited PCa cell proliferation. Finally, higher RAECsig scores predicted castration resistance in both primary and castration-resistant PCa. CONCLUSION: This study establishes an endothelial signature that links a subset of ECs to prostate cancer recurrence and castration resistance.

COLEC10 inhibits the stemness of hepatocellular carcinoma by suppressing the activity of ß-catenin signaling.

BACKGROUND: Liver cancer stem cells (CSCs) contribute to tumor initiation, progression, and recurrence in hepatocellular carcinoma (HCC). The Wnt/ß-catenin pathway plays a crucial role in liver cancer stemness, progression, metastasis, and drug resistance, but no clinically approved drugs have targeted this pathway efficiently so far. We aimed to elucidate the role of COLEC10 in HCC stemness. METHODS: The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases were employed to search for the association between COLEC10 expression and HCC stemness. Colony formation, sphere formation, side population, and limiting dilution tumor initiation assays were used to identify the regulatory role of COLEC10 overexpression in the stemness of HCC cell lines. Wnt/ß-catenin reporter assay and immunoprecipitation were performed to explore the underlying mechanism. RESULTS: COLEC10 level was negatively correlated with HCC stemness. Elevated COLEC10 led to decreased expressions of EpCAM and AFP (alpha-fetoprotein), two common markers of liver CSCs. Overexpression of COLEC10 inhibited HCC cells from forming colonies and spheres, and reduced the side population numbers in vitro, as well as the tumorigenic capacity in vivo. Mechanically, we demonstrated that overexpression of COLEC10 suppressed the activity of Wnt/ß-catenin signaling by upregulating Wnt inhibitory factor WIF1 and reducing the level of cytoplasmic ß-catenin. COLEC10 overexpression promoted the interaction of ß-catenin with the component of destruction complex CK1α. In addition, KLHL22 (Kelch Like Family Member 22), a reported E3 ligase adaptor predicted to interact with CK1α, could facilitate COLEC10 monoubiquitination and degradation. CONCLUSION: COLEC10 inhibits HCC stemness by downregulating the Wnt/ß-catenin pathway, which is a promising target for liver CSC therapy.

Optical coherence tomography characteristics and prognostic predictors of acute macular neuroretinopathy following SARS-CoV-2 infection.

PURPOSE: To analyze the characteristics of optical coherence tomography in acute macular neuroretinopathy (AMN) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and discuss the prognostic predictors. METHODS: Patients with AMN following SARS-CoV-2 infection were divided into two groups according to the presence or absence of hyperreflective outer nuclear layer (ONL) lesion involving the fovea. RESULTS: The first visit included 14 eyes in the fovea-involved group and 20 eyes in the no fovea-involved group. Ellipsoid zone (EZ) hyporeflection and interdigitation zone (IZ) interruption were detected in all eyes. Other common manifestations were myoid zone (MZ) hyperreflection (76.5%), ONL hyperreflection (73.5%), outer plexiform layer (OPL) thickening (64.7%), and EZ interruption (50%). The follow-up period was 48.4 ± 55.3 days. At the last visit, 12 eyes were in the fovea-involved group and 13 eyes in the no fovea-involved group. IZ interruption was detected in all eyes. Other common manifestations were EZ hyporeflection (92.0%), ONL atrophy (40.0%), OPL thickening (36.0%), OPL linear (32.0%), and MZ hyperreflection (32%). The improvement of visual acuity (VA) was -0.5 ± 0.5 and -0.2 ± 0.4 in the fovea-involved group and the no fovea-involved group, respectively, with a statistically significant difference between them (P = 0.045). Initial VA, initial cotton wool spot, initial ONL cyst, final ONL cyst, and final OPL linear were associated with final VA (P = 0.000, P = 0.029, P = 0.044, P = 0.049, P = 0.049, respectively). CONCLUSIONS: In the early stage of AMN following SARS-CoV-2 infection, IZ interruption and EZ hyporeflection were the most common manifestations, and pathology of IZ was more serious than that of EZ. Subsequently, OPL and ONL atrophied, and ONL atrophied faster. Regardless of whether hyperreflective ONL involved the fovea, VA improved, with a more noticeable improvement found in the fovea-involved group. The presence of initial ONL cyst and initial cotton wool spot, rapid atrophy of OPL, and poorer initial VA indicating poorer VA outcome.

CircPIAS1 promotes hepatocellular carcinoma progression by inhibiting ferroptosis via the miR-455-3p/NUPR1/FTH1 axis.

BACKGROUND: The role of circRNAs in hepatocellular carcinoma (HCC) progression remains unclear. CircPIAS1 (circBase ID: hsa_circ_0007088) was identified as overexpressed in HCC cases through bioinformatics analysis. This study aimed to investigate the oncogenic properties and mechanisms of circPIAS1 in HCC development. METHODS: Functional analyses were conducted to assess circPIAS1's impact on HCC cell proliferation, migration, and ferroptosis. Xenograft mouse models were employed to evaluate circPIAS1's effects on tumor growth and pulmonary metastasis in vivo. Bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays were utilized to elucidate the molecular pathways influenced by circPIAS1. Additional techniques, including RNA pulldown, fluorescence in situ hybridization (FISH), chromatin immunoprecipitation (ChIP), qPCR, and western blotting, were used to further explore the underlying mechanisms. RESULTS: CircPIAS1 expression was elevated in HCC tissues and cells. Silencing circPIAS1 suppressed HCC cell proliferation and migration both in vitro and in vivo. Mechanically, circPIAS1 overexpression inhibited ferroptosis by competitively binding to miR-455-3p, leading to upregulation of Nuclear Protein 1 (NUPR1). Furthermore, NUPR1 promoted FTH1 transcription, enhancing iron storage in HCC cells and conferring resistance to ferroptosis. Treatment with ZZW-115, an NUPR1 inhibitor, reversed the tumor-promoting effects of circPIAS1 and sensitized HCC cells to lenvatinib. CONCLUSION: This study highlights the critical role of circPIAS1 in HCC progression through modulation of ferroptosis. Targeting the circPIAS1/miR-455-3p/NUPR1/FTH1 regulatory axis may represent a promising therapeutic strategy for HCC.

Excitation generated preferential binding sites for ethane on porous carbon-copper porphyrin sorbents: ethane/ethylene adsorptive separation improved by light.

Energy-efficient separation of C2H6/C2H4 is a great challenge, for which adsorptive separation is very promising. C2H6-selective adsorption has big implications, while the design of C2H6-sorbents with ideal adsorption capability, particularly with the C2H6/C2H4-selectivity exceeded 2.0, is still challenging. Instead of the current strategies such as chemical modification or pore space modulation, we propose a new methodology for the design of C2H6-sorbents. With a Cu-TCPP [TCPP = 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin] framework dispersed onto a microporous carbon and a hierarchical-pore carbon, two composite sorbents are fabricated. The composite sorbents exhibit enhanced C2H6-selective adsorption capabilities with visible light, particularly the composite sorbent based on the hierarchical-pore carbon, whose C2H6 and C2H4 adsorption capacities (0 °C, 1 bar) are targetedly increased by 27% and only 1.8% with visible light, and therefore, an C2H6-selectivity (C2H6/C2H4 = 10/90, v/v) of 4.8 can be realized. With visible light, the adsorption force of the C2H6 molecule can be asymmetrically enhanced by the excitation enriched electron density over the adsorption sites formed via the close interaction between the Cu-TCPP and the carbon layer, whereas that of the C2H4 molecule is symmetrically altered and the forces cancelled each other out. This strategy may open up a new route for energy-efficient adsorptive separation of C2H6/C2H4 with light.

Efficacy of Shenglin decoction in preventing acute severe lymphocytopenia in patients with non-small cell lung cancer undergoing concurrent chemoradiotherapy: a study protocol for a randomized controlled trial.

Background: Definitive concurrent chemoradiotherapy (CCRT) followed by maintenance therapy with immune checkpoint inhibitors offers the best chance of cure for patients with stage III non-small cell lung cancer (NSCLC). A significant challenge in this regimen is the occurrence of acute severe lymphopenia (ASL), which can compromise treatment efficacy. Currently, there are no effective strategies for preventing and treating ASL. Shenglin decoction (SLD), a traditional Chinese herbal medicine formulation, has demonstrated preliminary efficacy in mitigating ASL. However, robust evidence from clinical trials and a clear understanding of its mechanism of action are still needed. This study aims to comprehensively assess the efficacy, safety, and underlying mechanisms of SLD in the prevention of ASL. Methods: This prospective, dual-center, open-label, randomized controlled trial will enroll 140 stage III NSCLC patients. Participants will be randomly allocated in a 1:1 ratio to a control group or an experimental group. Both groups will undergo definitive CCRT. Alongside the commencement of CCRT, the experimental group will receive an additional oral SLD intervention for a duration of three months. The primary outcome is the incidence rate of ASL, defined as the proportion of patients who experience at least one instance of a total lymphocyte count falling below 0.5 × 10^9 cells/L within 3 months of initiating CCRT treatment. Additionally, 16S rRNA gene sequencing analysis of fecal samples to assess gut microbiota, as well as metabolomic analysis of fecal/blood samples, will be conducted to explore potential mechanisms. Discussion: This study protocol aims to rigorously evaluate the efficacy and safety of SLD, as well as elucidate its mechanism of action in preventing ASL. Successful outcomes could establish SLD as an evidence-based intervention for ASL prevention in NSCLC patients undergoing CCRT. Trial Registration: The trial was registered at the Chinese Clinical Trials Registry (ChiCTR2300071788, https://www.chictr.org.cn/).

Construction of Nickel Single Atoms by Using the Inherent Confined Space in Template-Occupied Mesoporous Silica.

Due to their maximum atomic use of metal sites, single-atom catalysts (SACs) exhibit excellent catalytic activity in a variety of reactions. Although many techniques have been reported for the production of SACs, the construction of single atoms through a convenient strategy is still challenging. Here, we provide a facile method to prepare nickel SACs by utilizing the inherent confined space between the template and silica walls in template-occupied mesoporous silica KIT-6 (TOK). After the introduction of nickel-containing precursors into the inherent confined space of the TOK by solid-phase grinding, Ni SACs can be produced promptly during calcination. Single Ni atoms create a covalent Ni-O-Si structure in the TOK, as indicated by density functional theory (DFT) calculations and experimental data. This synthetic approach is easy to scale up, and 10 g of sample can be effortlessly synthesized using ball milling. The resultant Ni SACs were applied to the oxygen evolution reaction and exhibited higher catalytic activity and stability than the comparative sample synthesized in the absence of confined space.

Involvement of lncRNAs in the regulation of aerobic glycolysis in hepatocellular carcinoma: Main functions, regulatory mechanisms and potential therapeutic implications (Review).

Even under aerobic conditions, tumor cells can reprogram their metabolism to preferentially metabolize glucose into lactic acid. This abnormal metabolic pattern, known as the 'Warburg' effect or aerobic glycolysis, promotes cancer progression. Long non­coding RNAs (lncRNAs) are RNAs that are >200 nucleotides in length and do not have protein­coding capabilities. However, these RNAs play a key role in tumor development. There is increasing evidence to indicate that lncRNAs regulate glucose metabolism in tumor cells by affecting metabolic enzymes and some signaling pathways, thereby regulating the occurrence and progression of hepatocellular carcinoma (HCC). Therefore, it is crucial to understand which lncRNAs play a regulatory role in HCC glycolysis and to determine the related molecular mechanisms. The present review summarized and discussed the functions of lncRNAs, focusing on the regulatory mechanisms of lncRNAs in the process of glycolysis in HCC. In addition, the present review suggests the importance of lncRNAs as future therapeutic targets for antitumor cell metabolism.

Med1 inhibits ferroptosis and alleviates liver injury in acute liver failure via Nrf2 activation.

BACKGROUND: Extensive hepatocyte mortality and the absence of specific medical therapy significantly contribute to the unfavorable prognosis of acute liver failure (ALF). Ferroptosis is a crucial form of cell death involved in ALF. In this study, we aimed to determine the impact of Mediator complex subunit 1 (Med1) on ferroptosis and its potential hepatoprotective effects in ALF. RESULTS: Med1 expression is diminished in the liver of lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced ALF mice, as well as in hepatocytes damaged by H2O2 or TNF-α/D-GalN in vitro. Med1 overexpression mitigates liver injury and decreases the mortality rate of ALF mice by ferroptosis inhibition. The mechanism by which Med1 inhibits erastin-induced ferroptosis in hepatocytes involves the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant genes heme oxygenase-1 (HO-1), glutamate cysteine ligase catalytic (GCLC), and NAD(P)H quinone oxidoreductase 1 (NQO1). Furthermore, Med1 overexpression suppresses the transcription of proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the liver of mice with LPS/D-GalN-induced ALF. CONCLUSION: Overall, our research findings indicate that Med1 suppresses ferroptosis and alleviates liver injury in LPS/D-GalN-induced ALF through the activation of Nrf2. These findings substantiate the therapeutic viability of targeting the Med1-Nrf2 axis as a means of treating individuals afflicted with ALF.

Trends in application of fundus fluorescein angiography in fundus diseases during a recent ten-year period.

PURPOSE: To analyze the trends in the application of fundus fluorescein angiography (FFA) in fundus diseases over ten years. METHOD: It was a retrospective study. Patients who underwent FFA examinations between Jan 2012 and Dec 2021 in Eye Hospital of Wenzhou Medical University were included, excluding infants. Data included the fundus disease and examination time of FFA. RESULTS: A total of 37,038 cases underwent FFA examinations in our hospital in the past decade, and the number of each year was 3,628, 2,232, 2,230, 2,351, 3,546, 3,924, 5,325, 4,202, 4,432 and 5,168 from 2012 to 2021, respectively. The top three diseases were central serous chorioretinopathy (CSC), diabetic retinopathy (DR) and retinal vein occlusion (RVO) over the years from 2012 to 2021. The fourth to eighth ranked diseases were uveitis, age-related macular degeneration (AMD), choroidal neovascularization (CNV), optic neuropathy (ON) and polypoid choroidal vasculopathy (PCV) 9 years from 2012 to 2020; while retinal artery occlusion (RAO) ranked eighth and PCV fell out of the first eight in 2021. Tumor, Eale's disease, macular hemorrhage (MH), epiretinal retinal membrane (ERM) and Coat's disease had consistent proportions over the years. There was a significant statistical difference in the proportion of disease components over the years from 2012 to 2021(p = 0.000). CONCLUSION: Despite changes in annual distribution, CSC, DR, and RVO consistently ranked as the top three diseases requiring FFA examination. Changes might be related to the development of non-invasive fundus examination instruments and technologies. Indicated that FFA still hold its irreplaceable nature in diagnosing and understanding fundus diseases.

Quercetin Limits Tumor Immune Escape through PDK1/CD47 Axis in Melanoma.

Quercetin (3,3[Formula: see text],4[Formula: see text],5,7-pentahydroxyflavone) is a bioactive plant-derived flavonoid, abundant in fruits and vegetables, that can effectively inhibit the growth of many types of tumors without toxicity. Nevertheless, the effect of quercetin on melanoma immunology has yet to be determined. This study aimed to investigate the role and mechanism of the antitumor immunity action of quercetin in melanoma through both in vivo and in vitro methods. Our research revealed that quercetin has the ability to boost antitumor immunity by modulating the tumor immune microenvironment through increasing the percentages of M1 macrophages, CD8[Formula: see text] T lymphocytes, and CD4[Formula: see text] T lymphocytes and promoting the secretion of IL-2 and IFN-[Formula: see text] from CD8[Formula: see text] T cells, consequently suppressing the growth of melanoma. Furthermore, we revealed that quercetin can inhibit cell proliferation and migration of B16 cells in a dose-dependent manner. In addition, down-regulating PDK1 can inhibit the mRNA and protein expression levels of CD47. In the rescue experiment, we overexpressed PDK1 and found that the protein and mRNA expression levels of CD47 increased correspondingly, while the addition of quercetin reversed this effect. Moreover, quercetin could stimulate the proliferation and enhance the function of CD8[Formula: see text] T cells. Therefore, our results identified a novel mechanism through which CD47 is regulated by quercetin to promote phagocytosis, and elucidated the regulation of quercetin on macrophages and CD8[Formula: see text] T cells in the tumor immune microenvironment. The use of quercetin as a therapeutic drug holds potential benefits for immunotherapy, enhancing the efficacy of existing treatments for melanoma.

Corynoline Suppresses Osteoclastogenesis and Attenuates ROS Activities by Regulating NF-κB/MAPKs and Nrf2 Signaling Pathways.

Declining estrogen production in postmenopausal females causes osteoporosis in which the resorption of bone exceeds the increase in bone formation. Although clinical drugs are currently available for the treatment of osteoporosis, sustained medication use is accompanied by serious side effects. Corydalis bungeana Herba, a famous traditional Chinese herb listed in the Chinese Pharmacopoeia Commission, constitutes various traditional Chinese Medicine prescriptions, which date back to thousands of years. One of the primary active components of C. bungeana Turcz. is Corynoline (Cor), a plant isoquinoline alkaloid derived from the Corydalis species, which possesses bone metabolism disease therapeutic potential. The study aimed at exploring the effects as well as mechanisms of Cor on osteoclast formation and bone resorption. TRAcP staining, F-actin belt formation, and pit formation were employed for assessing the osteoclast function. Western blot, qPCR, network pharmacology, and docking analyses were used for analyzing the expression of osteoclast-associated genes and related signaling pathways. The study focused on investigating how Cor affected OVX-induced trabecular bone loss by using a mouse model. Cor could weaken osteoclast formation and function by affecting the biological receptor activators of NF-κB and its ligand at various concentrations. Mechanistically, Cor inhibited the NF-κB activation, and the MAPKs pathway stimulated by RANKL. Besides, Cor enhanced the protein stability of the Nrf2, which effectively abolished the RANKL-stimulated ROS generation. According to an OVX mouse model, Cor functions in restoring bone mass, improving microarchitecture, and reducing the ROS levels in the distal femurs, which corroborated with its in vitro antiosteoclastogenic effect. The present study indicates that Cor may restrain osteoclast formation and bone loss by modulating NF-κB/MAPKs and Nrf2 signaling pathways. Cor was shown to be a potential drug candidate that can be utilized for the treatment of osteoporosis.

Using an extended information-motivation-behavioral skills model to explain HPV vaccination intention among men who have sex with men only and men who have sex with men and women.

Men who have sex with men and women (MSMW) have been reported to differ in psychosocial and sexual behavior patterns from men who have sex with men only (MSMO). However, results regarding the differences in HPV vaccination intention/behavior were inconclusive. We compared HPV vaccination intention between MSMO and MSMW and analyzed the differences in potentially associated factors in China. MSM participants were recruited online using a snowball sampling method. Cross-sectional data were collected via a questionnaire based on the extended information-motivation-behavioral skills model. Structural equation modeling was conducted to examine the relationship between the variables, followed by multi-group analysis to test differences between groups. Of 914 MSM, 77.68% were MSMO and 22.32% were MSMW. MSMW had a higher rate of reluctance to vaccinate than MSMO (23.53% vs. 16.20%, p = .016). Differences between the two groups were statistically significant in risky sexual behavior, behavioral skills, and promotional attitude. In both groups, promotional attitude was the most significant predictor of vaccination intention. Vaccination intention was directly influenced by motivation and indirectly by risky sexual behavior in MSMO, but not significantly in MSMW. Additionally, the direct effect of information on behavioral skills in MSMW was significantly greater than that in MSMO, but we did not find any effect of behavioral skills on vaccination intention. MSMW had lower vaccination intention than MSMO. MSMO may be influenced by risky sexual behavior and motivation, positively impacting their vaccination intention, unlike MSMW. Targeted strategies could help promote HPV vaccination, especially in MSMW.

Comparison of the effect between traditional conservation and nasointestinal tube placement in adhesive small bowel obstruction: A matched case-control study.

Adhesive small bowel obstruction (ASBO) causes a major burden in emergency medicine. Owing to in situ decompression, nasointestinal tube (NIT) placement has been increasingly used in clinical practice compared with traditional conservation (TC); however, the indications remain controversial. This study was designed to explore the indications for each treatment in ASBOs and then suggest the optimal strategy. After propensity score matching, 128 pairs were included (the NIT and TC groups). The occurrence of severe adverse events (SAEs), peri-treatment clinical parameters, and radiological features were compared between the successful and failed treatment groups. According to different stages of the entire treatment, the independent risk factors for adverse effects for ASBO were analysed in phase I and phase II. In phase I, normal red blood cells (RBC) levels (p = 0.011) and a balanced sodium ion level (p = 0.016) positively affected the outcomes of TC treatment. In phase II, for the TC group, the successful treatment rate reached 79.5% for patients with ASBOs whose normal RBC levels (p = 0.006) or decreasing white blood cells (WBC) levels (p = 0.014) after treatment. For the NIT group, the treatment success rate was 68.1% for patients whose electrolyte imbalance could be reversed or whose neutrophil count/lymphocyte ratio (NLR) levels was lower than 4.3 (p = 0.018). TC treatment is highly recommended for patients with normal RBC counts and sodium levels pretreatment. After dynamic monitoring of the treatment process, for both the TC and NIT groups, once ASBOs had elevated inflammatory biomarkers or irreversible electrolyte disturbances, surgical interference was preferred.

Heimler syndrome with a complaint of blurred vision caused by compound heterozygous variants in PEX1.

INTRODUCTION: Heimler syndrome (HS) is a rare disorder that includes sensorineural hearing loss (SNHL), nail abnormalities, and enamel hypoplasia. Patients with this syndrome can also exhibit ocular manifestations. At present, only a few cases of HS have been reported, existing knowledge of this syndrome is limited, and many cases have been misdiagnosed or even missed. This is the first report of Heimler syndrome with blurred vision as the first complaint, which was diagnosed by genetic analysis in the ophthalmology department. CASE DESCRIPTION: An 8-year-old girl complained of bilateral visual blur and night blindness from birth. Ophthalmic examinations revealed bilateral retinitis pigmentosa with cystoid macular edema, visual impairment with hyperopia and astigmatism. Hearing test revealed bilateral severe sensorineural hearing loss. Dental examinations revealed enamel hypoplasia. In addition, whole-exome sequencing (WES) identified two pathogenic variants in PEX1: the previously reported missense variant c.2966T > C (p.I989 T), and the novel frameshift variant c.1671_1672del (p.G558Sfs*33). CONCLUSION: Heimler syndrome is caused by compound heterozygous PEX1 pathogenic variants, c.2966T > C (p.I989 T) and c.1671_1672del (p.G558Sfs*33), which contributed to the diversity of clinical and genetic profiles in this patient. The main clinical manifestations include bilateral retinitis pigmentosa with cystoid macular edema, sensorineural hearing loss, and enamel hypoplasia. Systemic examinations are suggested for patients suspected of having pigmentary retinal dystrophy, especially combined with hearing-related impairments. Genetic testing can help us to make a definitive diagnosis.

Ochratoxin A detoxification potentials of basil, chan, and chia seeds.

The most toxic of the ochratoxins is ochratoxin A (OTA), which is primarily produced by species of Aspergillus and Penicillium that can be found in maize, wheat, coffee, red wine, and various grains. OTA induces immunotoxicity, nephrotoxicity, hepatotoxicity, teratogenicity, and carcinogenicity in both animals and humans. Thus, there is a need to identify mycotoxin detoxification agents that can effectively decontaminate OTA. Seeds of basil (Ocimum basilicum L.), chan (Hyptis suaveolens L.), and chia (Salvia hispanica L.) are functional foods capable of eliminating harmful substances. Despite this potential, the impact of these seeds on OTA detoxification remains unclear. This study reveals that milled basil, chan, and chia seeds adsorb significant levels of OTA, with chia demonstrating the highest adsorption capacity, followed by chan and basil seeds showing the least efficiency. Furthermore, milled basil, chan, and chia seeds effectively reduced OTA residues in artificial gastric and intestinal fluids, where they achieved up to 93% OTA adsorption in the former. In addition, these milled seeds were able to remove OTAs from canned, drip, and instant coffee. This study is the first to report the OTA elimination potential of basil, chan, and chia seeds.

Cinnamaldehyde Alleviates Bone Loss by Targeting Oxidative Stress and Mitochondrial Damage via the Nrf2/HO-1 Pathway in BMSCs and Ovariectomized Mice.

Osteoporosis (OP) is typically brought on by disruption of bone homeostasis. Excessive oxidative stress and mitochondrial dysfunction are believed to be the primary mechanisms underlying this disorder. Therefore, in order to restore bone homeostasis effectively, targeted treatment of oxidative stress and mitochondrial dysfunction is necessary. Cinnamaldehyde (CIN), a small molecule that acts as an agonist for the nuclear factor erythroid 2-related factor (Nrf2), has been found to possess antiapoptotic, anti-inflammatory, and antioxidant properties. We found that CIN, while rescuing apoptosis, can also reduce the accumulation of reactive oxygen species (ROS) to improve mitochondrial dysfunction and thus restore the osteogenic differentiation potential of BMSCs disrupted by hydrogen peroxide (H2O2) exposure. The role of CIN was preliminarily considered to be a consequence of Nrf2/HO-1 axis activation. The ovariectomized mice model further demonstrated that CIN treatment ameliorated oxidative stress in vivo, partially reversing OVX-induced bone loss. This improvement was seen in the trabecular microarchitecture and bone biochemical indices. However, when ML385 was concurrently injected with CIN, the positive effects of CIN were largely blocked. In conclusion, this study sheds light on the intrinsic mechanisms by which CIN regulates BMSCs and highlights the potential therapeutic applications of these findings in the treatment of osteoporosis.

Mesenchymal stem cell-regulated miRNA-mRNA landscape in acute-on-chronic liver failure.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a major challenge in the field of hepatology. While mesenchymal stem cell (MSC) therapy can improve the prognosis of patients with ACLF, the molecular mechanisms through which MSCs attenuate ACLF remain poorly understood. We performed global miRNA and mRNA expression profiling via next-generation sequencing of liver tissues from MSC-treated ACLF mice to identify important signaling pathways and major factors implicated in ACLF alleviation by MSCs. METHODS: Carbon tetrachloride-induced ACLF mice were treated with saline or mouse bone marrow-derived MSCs. Mouse livers were subjected to miRNA and mRNA sequencing. Related signal transduction pathways were obtained through Gene Set Enrichment Analysis. Functional enrichment, protein-protein interaction, and immune infiltration analyses were performed for the differentially expressed miRNA target genes (DETs). Hub miRNA and mRNA associated with liver injury were analyzed using LASSO regression. The expression levels of hub genes were subjected to Pearson's correlation analysis and verified using RT-qPCR. The biological functions of hub genes were verified in vitro. RESULTS: The tricarboxylic acid cycle and peroxisome proliferator-activated receptor pathways were activated in the MSC-treated groups. The proportions of liver-infiltrating NK resting cells, M2 macrophages, follicular helper T cells, and other immune cells were altered after MSC treatment. The expression levels of six miRNAs and 10 transcripts correlated with the degree of liver injury. miR-27a-5p was downregulated in the mouse liver after MSC treatment, while its target gene E2f2 was upregulated. miR-27a-5p inhibited E2F2 expression, suppressed G1/S phase transition and proliferation of hepatocytes, in addition to promoting their apoptosis. CONCLUSIONS: This is the first comprehensive analysis of miRNA and mRNA expression in the liver tissue of ACLF mice after MSC treatment. The results revealed global changes in hepatic pathways and immune subpopulations. The miR-27a-5p/E2F2 axis emerged as a central regulator of the MSC-induced attenuation of ACLF. The current findings improve our understanding of the molecular mechanisms through which MSCs alleviate ACLF.

Comparative efficacy of aflibercept and ranibizumab in the treatment of age-related macular degeneration with retinal pigment epithelial detachment: a systematic review and network meta-analysis.

OBJECTIVES: To evaluate the efficacy of anti-vascular endothelial growth factor (VEGF) in treatment of age-related macular degeneration (AMD) with retinal pigment epithelial detachment (PED). METHODS: Systematic review identifying studies comparing intravitreal ranibizumab (IVR), intravitreal aflibercept (IVA) and intravitreal conbercept (IVC) published before Mar 2022. RESULTS: One randomized controlled trial and 6 observational studies were selected for meta-analysis (1,069 patients). The change of best corrected visual acuity (BCVA) in IVA 2.0 mg group was better than IVR 0.5 mg (average difference 0.07) and IVR 2.0 mg (average difference 0.10), the differences were statistically significant. The change of the height of PED in IVA 2.0 group was better than IVR 0.5 group (average difference 45.30), the difference was statistically significant. The proportion of patients without PED at last visit in IVA 2.0 group were better than those in IVR 2.0 group (hazard ratio 1.91), the difference was statistically significant. There was no significant difference compared with IVR 0.5 group (hazard ratio 1.45). IVA required fewer injections than IVR, with a mean difference of -1.58. CONCLUSIONS: IVA appears to be superior to IVR in improvement of BCVA, height decrease of PED and regression of PED with less injections in nAMD with PED.