Emerging ferroptosis inhibitors as a novel therapeutic strategy for the treatment of neonatal hypoxic-ischemic encephalopathy.

Neonatal hypoxia-ischemia encephalopathy (NHIE), an oxygen deprivation-mediated brain injury due to birth asphyxia or reduced cerebral blood perfusion, often leads to lifelong sequelae, including seizures, cerebral palsy, and mental retardation. NHIE poses a significant health challenge, as one of the leading causes of neonatal morbidity and mortality globally. Despite this, available therapies are limited. Numerous studies have recently demonstrated that ferroptosis, an iron-dependent non-apoptotic regulated form of cell death characterized by lipid peroxidation (LPO) and iron dyshomeostasis, plays a role in the genesis of NHIE. Moreover, recently discovered compounds have been shown to exert potential therapeutic effects on NHIE by inhibiting ferroptosis. This comprehensive review summarizes the fundamental mechanisms of ferroptosis contributing to NHIE. We focus on various emerging therapeutic compounds exhibiting characteristics of ferroptosis inhibition and delineate their pharmacological benefits for the treatment of NHIE. This review suggests that pharmacological inhibition of ferroptosis may be a potential therapeutic strategy for NHIE.

"Severe blepharoptosis correction with the fixation of levator complex and conjoint fascial sheath: 12 Years of Experience in a Single Center."

BACKGROUND: The correction of severe blepharoptosis is one of the most challenging surgeries in plastic surgery. This study introduces a novel self-reinforced fixation technique combining the levator complex with conjoint fascial sheath for the correction of severe blepharoptosis and reviews the postoperative results over the preceding 12 years. METHODS: This retrospective review included all patients who underwent self-reinforced fixation with or without conjoint fascial sheath at the authors' center between 2010 and 2022. The clinical data of the two groups were collected and evaluated. RESULTS: All patients were followed up for 6 months to 8 years postoperatively. The mean postoperative MRD1 and LF increased significantly in both groups. Sufficient correction of ptosis was achieved in 32 (65.31%) and 84 (81.56%) eyelids in Groups I and II, respectively. The mean eyelid lagophthalmos was 1.27± 0.91 mm and 0.85 ± 0.89 mm in Groups I and II, respectively. The most common complication was undercorrection of ptosis, which was observed in 14 eyelids (28.57%) and 15 eyelids (14.56%) in Groups I and II, respectively. CONCLUSIONS: The self-reinforced fixation technique was effective in correcting severe congenital ptosis in Chinese patients. The clinical effect was consistent in the long-term follow-up cases, and the recurrence rate was low. Thus, this technique can enhance the strength of the levator muscle and maintain appropriate elasticity of eye closure. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

A mild protocol for efficient preparation of functional molecules containing triazole.

The construction of a class of novel triazole molecules containing sulfonyl fluoride functionalities was achieved through Cu-catalyzed click chemistry in good to excellent yields. The sulfonyl fluoride moieties were cleaved completely under base conditions to produce N-unsubstituted triazoles quantitatively, which provides a strategy to combine SuFEx click chemistry with Cu-catalyzed click chemistry ingeniously.

[Analysis of risk factors for congenital auriclar deformity and its different types].

Objective:To Explore the clinical characteristics,risk factors,and differences in risk factors for different types of congenital auricular deformities,in order to provide theoretical basis for precise prevention and control of congenital auriclar deformity. Methods:Full-term newborns born in the Second Affiliated Hospital of Zhengzhou University from May 2022 to January 2023 were screened for auricle malformation, general information and data were collected,,and high-risk factors were investigated withself-made questionnaire.Using a case-control study method,newborns with auriclar deformities were selected as the case group and those without auriclar deformities during the same period were selected as the control group.A case-control study was conducted to analyze the incidence rate,high-risk factors,and differences in high-risk factors for different types of auricle deformities. Results:A total of 1 758 newborns （3 516 ears） were included in this study,including 562 newborns（927 ears） with auriclar deformities,the incidence of congenital malformations of the auricle is 26.37%.Among them,289 ears （8.22%） were helical rim deformity,244 ears （6.94%） were lidding/lop ear,166 ears （4.72%） were mixed deformities,131 ears （3.73%） were prominent/cup ear,79 ears （2.25%） were Stahl's ears,16 ears （0.46%） were abnormal conchal crus,and 2 ears （0.06%） were cryptotia.Maternal history of infection in early pregnancy（OR=1.513，95%CI 1.119-2.045）,previous miscarriage history（OR=1.300，95%CI 1.049-1.613）,and abnormal pregnancy（OR=1.278，95%CI 1.032-1.582） are risk factors for congenital auricular malformations.There was no statistically significant difference in the history of infection（χ²=1.877，P=0.391）,previous miscarriage（χ²=4.706，P=0.095）,and abnormal pregnancy（χ²=5.026，P=0.081） among mothers with helical rim deformity,lidding/lop ear,and mixed deformities. Conclusion:The incidence rate of congenital auricle deformity is high, with common malformations such as helical rim deformity, lidding/lop ear,and mixed deformities. Congenital auricular deformity is caused by various factors, the same risk factor has roughly the same impact on different types of morphological abnormalities.

The Medial Canthus Fibrous Band's Impact on Epicanthal Fold Severity and Classification in Asians: Implications for Epicanthoplasty.

BACKGROUND: The epicanthal fold (EF) is a semilunar skin fold located in the medial canthus in most Asians. The medial canthus fibrous band (MCFB) reportedly plays a critical role in EF formation. Variations in MCFB shape and size affect the severity and type of EF. OBJECTIVES: We aimed to analyze MCFB variations in different types and severities of EF and explore the effect of the MCFB resection epicanthoplasty technique (MCFB epicanthoplasty). METHODS: Surgical videos of 40 patients undergoing MCFB epicanthoplasty in our department were reviewed. The MCFB (area), transverse dimension, vertical dimension, upper eyelid direction length (UEDL), and lower eyelid direction length (LEDL) were measured. For aesthetic assessment, 37 patients were followed up for 6 months; intercanthal distance (ICD) and horizontal lid fissure length (HLFL) were measured. Preoperative and postoperative ICD/HLFL ratios were compared. Postoperative scar recovery was evaluated with the Patient and Observer Scar Assessment Scale. Statistical significance was set at P < .05. RESULTS: The MCFB diameter and area were larger for severe EF than for moderate EF (P < .01). Patients with severe EF had larger LEDL than UEDL (P < .01). The tarsalis type had a larger LEDL than the palpebralis type with the same severity (P < .01). MCFB epicanthoplasty yielded favorable postoperative cosmetic effects and scar recovery. Postoperative ICD decreased, while HLFL increased compared to preoperative values (P < .001). The ICD/HLFL ratio was significantly lower postoperatively than preoperatively (P < .001). Postoperative ICD/HLFL ratio was 1.2:1. CONCLUSIONS: The MCFB affects the severity and type of EF. MCFB epicanthoplasty effectively corrected moderate to severe EF.

RNA-binding proteins in breast cancer: Biological implications and therapeutic opportunities.

RNA-binding proteins (RBPs) refer to a class of proteins that participate in alternative splicing, RNA stability, polyadenylation, localization and translation of RNAs, thus regulating gene expression in post-transcriptional manner. Dysregulation of RNA-RBP interaction contributes to various diseases, including cancer. In breast cancer, disorders in RBP expression and function influence the biological characteristics of tumor cells. Targeting RBPs has fostered the development of innovative therapies for breast cancer. However, the RBP-related mechanisms in breast cancer are not completely clear. In this review, we summarize the regulatory mechanisms of RBPs and their signaling crosstalk in breast cancer. Specifically, we emphasize the potential of certain RBPs as prognostic factors due to their effects on proliferation, invasion, apoptosis, and therapy resistance of breast cancer cells. Most importantly, we present a comprehensive overview of the latest RBP-related therapeutic strategies and novel therapeutic targets that have proven to be useful in the treatment of breast cancer.

Lichen planus pemphigoides induced by anti-PD-1 antibody: A case only involved in oral mucosa with excellent topical treatment efficiency.

Lichen planus pemphigoides (LPP) is a rare autoimmune subepidermal disease that can occur in patients receiving immune checkpoint inhibitors. Its clinical manifestations are combined with the characteristics of lichen planus with bullous pemphigoid that can occur on either skin or oral mucosa. It should be noted that oral LPP is very rare. Here, we report a novel case of oral LPP induced by an anti-PD-1 agent. The patient presented with typical clinical features in oral mucosa, and the diagnosis was based on histopathology and immunological studies. Given that the patient was receiving an anti-PD-1 agent, topical therapy was chosen, and a nice therapeutic effect was obtained. No significant recurrence was observed after a 2-year follow-up. A good and stable therapeutic effect achieved by rapid and local symptomatic medication suggests that accurate and sensitive diagnosis is necessary.

Effectiveness of physical activity interventions for core symptoms of autism spectrum disorder: A systematic review and meta-analysis.

In this paper, systematic review and meta-analysis were used to demonstrate the effectiveness of physical activity intervention on core symptoms of autism spectrum disorder (ASD). Physical activity intervention for core symptoms of ASD were retrieved by computer from the PubMed Cochrane Library, Web of Science, APA PsycNet, and CNKI database during December 1, 2022. Two researchers evaluated the quality of the included literature and extracted the data. Sixteen studies were eventually included, with a total of 587 patients with ASD. Meta-analysis showed that the core symptoms of ASD patients decreased after physical activity intervention, ES(g) = 0.681(95% CI: 0.380-0.982, p = 0.000), specifically, physical activity improved the reduction of social disorder ES(g) = 0.749(95% CI: 0.524-0.973) and repeated rigid behavior ES(g) = 0.553 (95% CI: -0.079 to 1.186). Subgroup analysis showed that preschool children with ASD who were 3-6 years old, exercised for more than 12 weeks, more than 3 times a week, and exercised for more than 90 min per session had better improvement in core symptoms after participating in physical activity. The conclusion of this paper is that physical activity intervention can improve the core symptoms of ASD, especially the reduction of social disorders and repetitive behaviors.

Abnormal Expression of Prolyl Oligopeptidase (POP) and Its Catalytic Products Ac-SDKP Contributes to the Ovarian Fibrosis Change in Polycystic Ovary Syndrome (PCOS) Mice.

Polycystic ovary syndrome (PCOS) is an endocrine disorder and metabolic syndrome. Ovarian fibrosis pathological change in PCOS has gradually attracted people's attention. In this study, we constructed a PCOS mouse model through the use of dehydroepiandrosterone. Sirius red staining showed that the ovarian tissues in PCOS mice had obvious fibrosis. Prolyl oligopeptidase (POP) is a serine protease and N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is its catalytic product. Studies show that abnormal expression and activity of POP and Ac-SDKP are closely related to tissue fibrosis. It was found that the expression of POP and Ac-SDKP was decreased in the ovaries of PCOS mice. Further studies showed that POP and Ac-SDKP promoted the expression of matrix metalloproteinases 2 (MMP-2) expression and decreased the expression of transforming growth factor beta 1 (TGF-ß1) in granulosa cells. Hyperandrogenemia is a typical symptom of PCOS. We found that testosterone induced the low expression of POP and MMP2 and high expression of TGF-ß1 in granulosa cells. POP overexpression and Ac-SDKP treatment inhibited the effect of testosterone on TGF-ß1 and MMP2 in vitro and inhibited ovarian fibrosis in the PCOS mouse model. In conclusion, PCOS ovarian tissue showed obvious fibrosis. Low expression of POP and Ac-SDKP and changes in fibrotic factors contribute to the ovarian pathological fibrosis induced by androgen.

Significant efficacy of short-course, low-concentration betamethasone mouthwash therapy for severe erosive oral lichen planus: a randomized controlled trial.

OBJECTIVES: To evaluate the short-term efficacy of low-concentration betamethasone mouthwash for severe erosive oral lichen planus (EOLP). MATERIALS AND METHOD: In this randomized, investigator-blind, positive-controlled trial, OLP patients with erosive lesions received betamethasone mouthwash (0.137 mg/mL) or dexamethasone mouthwash (0.181 mg/mL) three times daily for 2 or 4 weeks and were followed up for 3 months to observe recurrence. The primary outcome was the week-2 reduction in erosive area. RESULTS: Fifty-seven participants were randomized to betamethasone (n = 29) and dexamethasone (n = 28). At week 2, participants using betamethasone (n = 28) experienced a greater reduction in erosive area than gargling with dexamethasone (n = 26). Similarly, secondary outcomes, including the healing proportion of erosions, reduced pain level, reduction in atrophic area, Thongprasom score, and recurrence interval, showed the superiority of betamethasone. At week 4, betamethasone (n = 7) was not superior to dexamethasone (n = 15) in further reducing lesional area and pain level. No serious adverse events were documented. CONCLUSIONS: The 0.137 mg/mL compound betamethasone mouthwash exhibited significant efficacy in rapidly enhancing erosion healing within 2 weeks and extending the recurrence interval with a good safety profile. CLINICAL RELEVANCE: This study proved the significant efficacy of short-course 0.137 mg/mL betamethasone mouthwash therapy for treating erosion and pain, providing a novel topical agent for patients with severe EOLP. TRIAL REGISTRATION: This study was prospectively registered at the International Clinical Trials Registry Platform ( ChiCTR1800016507 ) on 5 June 2018.

Using a Generalized Logistic Regression Method to Detect Differential Item Functioning With Multiple Groups in Cognitive Diagnostic Tests.

Items with the presence of differential item functioning (DIF) will compromise the validity and fairness of a test. Studies have investigated the DIF effect in the context of cognitive diagnostic assessment (CDA), and some DIF detection methods have been proposed. Most of these methods are mainly designed to perform the presence of DIF between two groups; however, empirical situations may contain more than two groups. To date, only a handful of studies have detected the DIF effect with multiple groups in the CDA context. This study uses the generalized logistic regression (GLR) method to detect DIF items by using the estimated attribute profile as matching criteria. A simulation study is conducted to examine the performance of the two GLR methods, GLR-based Wald test (GLR-Wald) and GLR-based likelihood ratio test (GLR-LRT), in detecting the DIF items, the results based on the ordinary Wald test are also reported. Results show that (1) both GLR-Wald and GLR-LRT have more reasonable performance in controlling Type I error rates than the ordinary Wald test in most conditions; (2) the GLR method also produces higher empirical rejection rates than the ordinary Wald test in most conditions; and (3) using the estimated attribute profile as the matching criteria can produce similar Type I error rates and empirical rejection rates for GLR-Wald and GLR-LRT. A real data example is also analyzed to illustrate the application of these DIF detection methods in multiple groups.

Surface warming from altitudinal and latitudinal amplification over Antarctica since the International Geophysical Year.

Warming has been and is being enhanced at high latitudes or high elevations, whereas the quantitative estimation for warming from altitude and latitude effects has not been systematically investigated over Antarctic Ice Sheet, which covers more than 27 degrees of latitude and 4000 m altitude ranges. Based on the monthly surface air temperature data (1958-2020) from ERA5 reanalysis, this work aims to explore whether elevation-dependent warming (EDW) and latitude-dependent warming (LDW) exist. Results show that both EDW and LDW have the cooperative effect on Antarctic warming, and the magnitude of EDW is stronger than LDW. The negative EDW appears between 250 m and 2500 m except winter, and is strongest in autumn. The negative LDW occurs between 83 °S and 90 °S except in summer. Moreover, the surface downward long-wave radiation that related to the specific humidity, total cloud cover and cloud base height is a major contributor to the EDW over Antarctica. Further research on EDW and LDW should be anticipated to explore the future Antarctic amplification under different emission scenarios.

Down-regulation of DNA key protein-FEN1 inhibits OSCC growth by affecting immunosuppressive phenotypes via IFN-γ/JAK/STAT-1.

Oral squamous cell carcinoma (OSCC) escape from the immune system is mediated through several immunosuppressive phenotypes that are critical to the initiation and progression of tumors. As a hallmark of cancer, DNA damage repair is closely related to changes in the immunophenotypes of tumor cells. Although flap endonuclease-1 (FEN1), a pivotal DNA-related enzyme is involved in DNA base excision repair to maintain the stability of the cell genome, the correlation between FEN1 and tumor immunity has been unexplored. In the current study, by analyzing the clinicopathological characteristics of FEN1, we demonstrated that FEN1 overexpressed and that an inhibitory immune microenvironment was established in OSCC. In addition, we found that downregulating FEN1 inhibited the growth of OSCC tumors. In vitro studies provided evidence that FEN1 knockdown inhibited the biological behaviors of OSCC and caused DNA damage. Performing multiplex immunohistochemistry (mIHC), we directly observed that the acquisition of critical immunosuppressive phenotypes was correlated with the expression of FEN1. More importantly, FEN1 directly or indirectly regulated two typical immunosuppressive phenotype-related proteins human leukocyte antigen (HLA-DR) and programmed death receptor ligand 1 (PD-L1), through the interferon-gamma (IFN-γ)/janus kinase (JAK)/signal transducer and activator transcription 1 (STAT1) pathway. Our study highlights a new perspective on FEN1 action for the first time, providing theoretical evidence that it may be a potential immunotherapy target for OSCC.

Role of the Medial Canthus Fibrous Band in Forming Moderate and Severe Epicanthal Folds in Asians and Its Clinical Application.

BACKGROUND: Epicanthal folds (EFs) are skin folds located at the medial canthus in Asians. However, the anatomical structure of EFs remains unclear. We discovered a fibrous band connected to the medial canthal tendon (MCT) and referred to it as the medial canthal fibrous band (MCFB). This study aimed to verify whether the MCFB is different from the MCT and whether its unique anatomical relationship with the MCT plays an important role in EF formation. METHODS: Forty patients who underwent epicanthoplasty from February 2020 to October 2021 were included. EFs from 11 patients underwent biopsy and was stained with hematoxylin and eosin, Masson's trichrome, and Weigert's stains to reveal their composition. Expression of collagens I and III and elastin was determined through immunohistochemical staining, and their mean optical density was measured. Preoperative and immediate exposed lacrimal caruncle area (ELCA) was measured after removing MCFB. RESULTS: MCFB is a fibrous tissue located in the EF and above the MCT. The orientation and composition of collagen fibers of the MCFB are different from those of the MCT (P < 0.001). The MCFB also has more elastin fibers than the MCT (P < 0.05). Immediate ELCA was significantly higher than pre-ELCA (P < 0.001) once MCFB was removed. CONCLUSIONS: The MCFB is composed of collagen fibers different from those in the MCT and plays a role in EF formation. Removing the MCFB during epicanthoplasty can result in a more attractive appearance postoperatively.

Biofilm-Based Biocatalysis for Galactooligosaccharides Production by the Surface Display of ß-Galactosidase in Pichia pastoris.

Galactooligosaccharides (GOS) are one of the most important functional oligosaccharide prebiotics. The surface display of enzymes was considered one of the most excellent strategies to obtain these products. However, a rough industrial environment would affect the biocatalytic process. The catalytic process could be efficiently improved using biofilm-based fermentation with high resistance and activity. Therefore, the combination of the surface display of ß-galactosidase and biofilm formation in Pichia pastoris was constructed. The results showed that the catalytic conversion rate of GOS was up to 50.3% with the maximum enzyme activity of 5125 U/g by screening the anchorin, and the number of the continuous catalysis batches was up to 23 times. Thus, surface display based on biofilm-immobilized fermentation integrated catalysis and growth was a co-culture system, such that a dynamic equilibrium in the consolidated integrative process was achieved. This study provides the basis for developing biofilm-based surface display methods in P. pastoris during biochemical production processes.

Community differentiation of rhizosphere microorganisms and their responses to environmental factors at different development stages of medicinal plant Glehnia littoralis.

Rhizosphere microorganisms play a key role in affecting plant quality and productivity through its interaction with plant root system. To figure out the bottleneck of the decline of yield and quality in the traditional Chinese medicinal herbs Glehnia littoralis they now encounter, it is important to study the dynamics of rhizosphere microbiota during the cultivation of G. littoralis. In the present study, the composition, diversity and function of rhizosphere microbes at different development stages of G. littoralis, as well as the correlation between rhizosphere microbes and environmental factors were systematically studied by high-throughput sequencing. There were significant differences between the rhizosphere microbes at early and middle-late development stages. More beneficial bacteria, such as Proteobacteria, and more symbiotic and saprophytic fungi were observed at the middle-late development stage of G. littoralis, while beneficial bacteria such as Actinobacteria and polytrophic transitional fungi were abundant at all development stages. The results of redundancy analysis show that eight environmental factors drive the changes of microflora at different development stages. pH, soil organic matter (SOM) and available phosphorus (AP) had important positive effects on the bacterial and fungal communities at the early development stage; saccharase (SC) and nitrate nitrogen (NN) showed significant positive effects on the bacterial and fungal communities at the middle and late stages; while urease (UE), available potassium (AK), and alkaline phosphatase (AKP) have different effects on bacterial and fungal communities at different development stages. Random forest analysis identified 47 bacterial markers and 22 fungal markers that could be used to distinguish G. littoralis at different development stages. Network analysis showed that the rhizosphere microbes formed a complex mutualistic symbiosis network, which is beneficial to the growth and development of G. littoralis. These results suggest that host development stage and environmental factors have profound influence on the composition, diversity, community structure and function of plant rhizosphere microorganisms. This study provides a reference for optimizing the cultivation of G. littoralis.

Identification and Biological Validation of a Chemokine/Chemokine Receptor-Based Risk Model for Predicting Immunotherapeutic Response and Prognosis in Head and Neck Squamous Cell Carcinoma.

Over 80% of head and neck squamous cell carcinoma (HNSCC) patients failed to respond to immunotherapy, which can likely be attributed to the tumor microenvironment (TME) remolding mediated by chemokines/chemokine receptors (C/CR). This study aimed to establish a C/CR-based risk model for better immunotherapeutic responses and prognosis. After assessing the characteristic patterns of the C/CR cluster from the TCGA-HNSCC cohort, a six-gene C/CR-based risk model was developed to stratify patients by LASSO Cox analysis. The screened genes were multidimensionally validated by RT-qPCR, scRNA-seq, and protein data. A total of 30.4% of patients in the low-risk group had better responses to anti-PD-L1 immunotherapy. A Kaplan-Meier analysis showed that patients in the low-risk group had longer overall survival. A time-dependent receiver operating characteristic curve and Cox analyses indicated that risk score served as an independent predictive indicator. The robustness of the immunotherapy response and prognosis prediction was also validated in independent external datasets. Additionally, the TME landscape revealed that the low-risk group was immune activated. Furthermore, the cell communication analysis on the scRNA-seq dataset revealed that cancer-associated fibroblasts were the main communicators within the C/CR ligand-receptor network of TME. Collectively, The C/CR-based risk model simultaneously predicted immunotherapeutic response and prognosis, potentially optimizing personalized therapeutic strategies of HNSCC.