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Jing Peng,* Lei Zhang,* Chenwei Yuan, Liheng Zhou, Shuguang Xu, Yanping Lin, Jie Zhang, Wenjin Yin, Jinsong Lu Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: The estrogen receptor (ER)-positive subtype of breast cancer (BC) is the most common type of BC. A number of long noncoding RNAs (lncRNAs) play critical roles in cancer biology, including BC. Previous lncRNA profiling studies have focused only on triple-negative BC and HER 2-positive BC, and no studies have specifically focused on lncRNAs in ER-positive BC. In this study, we analyzed the expression profile of the lncRNAs and mRNAs found in this particular subtype of BC for the first time.Methods: We evaluated lncRNA microarray data from four pairs of primary BC and adjuvant nontumor breast tissues. Then, we screened out the differently expressed genes and measured the correlation of the expression levels of lncRNAs and ERalpha by Pearson’s correlation coefficient analysis. We also performed classification and length distribution of the dysregulated lncRNAs. KEGG pathway analysis was used to understand the biological roles of these differently expressed genes. lncRNA–mRNA coexpression networks were constructed. Finally, RT-PCR was employed to validate the microarray analysis findings.Results: We screened out 2,178 differently expressed lncRNAs, and 13 lncRNAs were found to be associated with the ER expression level. Classification analysis showed that most lncRNAs belonged to intergenic lncRNA and were from 400 to 800 nt in length. Chromosome distribution showed that many of the lncRNAs were mapped to chromosome 1. In the pathway analysis, most of the genes were related to cancer-associated behaviors, such as p53 signaling pathway, cell cycle, focal adhesion, and ECM–receptor interaction. lncRNA–mRNA coexpression networks were constructed, and the lncRNAs related to ESR1, BRCA1, and BRCA2 in the two groups were significantly different. The RT-PCR results were consistent with the data obtained from the microarrays.Conclusion: These results provide useful information for exploring potential novel biomarkers as diagnosis and therapy targets for the clinical treatment of ER-positive BC. Keywords: breast cancer, long noncoding RNA, estrogen receptor

Aim: To study the causal relationship between obesity-related anthropometric traits and myopia and the mediating role of educational attainment (EA)., Methods: Univariable Mendelian randomization (UVMR) was performed to evaluate the causal association between body mass index (BMI), height, waist-hip ratio (WHR, adjusted for BMI), and mean spherical equivalent (MSE). BMI was divided into fat and fat-free mass and included in multivariable Mendelian randomization (MVMR) to explore the roles of different BMI components in the causal relationship between BMI and MSE. A mediation analysis based on two-step Mendelian randomization (MR) was carried out. Specifically, UVMR was conducted to estimate the causal effect of BMI on EA. The direct effect of EA on MSE was estimated from MVMR. The mediation effect of EA in the BMI-EA-MSE model was calculated by the product of coefficients method. Expression quantitative trait loci (eQTL)-MR, reverse MR, and Linkage Disequilibrium Score Regression (LDSC) were performed to assess the robustness., Results: Genetically predicted higher BMI had a positive total effect on MSE ( β IVW=0.26 D, 95%CI=0.14 to 0.37 D, P <0.001), whereas there was no significant association between height, WHR, and MSE. Fat mass was found to play a significant role in the effect of body mass on MSE ( β IVW=0.50 D, 95%CI=0.21 to 0.78 D, P =0.001), but there was no significant association between fat-free mass and MSE. The causal effect of BMI on EA was -0.14 (95%CI=-0.16 to -0.11, P <0.001), and the direct effect of EA on MSE was -0.63 D (95%CI=-0.81 to -0.44 D, P <0.001). The mediating effect of EA in the BMI-EA-MSE model was 0.09 D (95%CI=0.06 to 0.12 D), with a mediation proportion of 33% (95%CI=22.1% to 44.6%). No reverse causal associations were detected except for BMI on EA. The results of eQTL-MR and LDSC were consistent with each MR analysis., Conclusion: Genetically predicted higher BMI decreases the degree of myopia with a 33% mediation proportion by EA, and fat mass provides a dominant protective role in body mass-myopia. As a supplement to previous observational studies, it provides strong evidence for the relationship between anthropometric traits and refractive errors and offers a theoretical basis for future measures to prevent and control myopia., Competing Interests: Conflicts of Interest: Lu Y, None; Zhang CC, None; Ma RT, None; Li YJ, None; Li WP, None; Hu DWJ, None; Zhou LH, None., (International Journal of Ophthalmology Press.)

Jianghua Kucha (JHKC) is an ancient tea germplasm, which presents a high value for resource utilization but was less developed in aroma research. In this study, volatile metabolites in fresh leaves and corresponding black teas of JHKC, along with odorants of JHKC black teas were systematically investigated using stir-bar sorptive extraction in combination with gas chromatography-mass spectrometry (GC-MS) and GC-olfactometry/MS (GC-O/MS) technologies. A total of 128 and 135 volatile compounds were identified in fresh leaves and black teas, respectively, along with 13 key differential volatile components derived from fatty acids, pigments, glycoside precursors, and the terpene pathway. An odorant wheel for JHKC black teas was developed based on 29 important odorants determined through a combination of GC-O/MS perception, aroma extract dilution analysis, odor activity value measurement. trans-β-Damascenone, cis-jasmone, and cis-jasmin lactone have been identified as significant contributors to the "sweet" flavor of JHKC black teas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Mitochondrial dysfunction is linked to myocardial ischemia-reperfusion (I/R) injury. Checkpoint kinase 1 (CHK1) could facilitate cardiomyocyte proliferation, however, its role on mitochondrial function in I/R injury remains unknown., Methods: To investigate the role of CHK1 on mitochondrial function following I/R injury, cardiomyocyte-specific knockout/overexpression mouse models were generated. Adult mouse cardiomyocytes (AMCMs) were isolated for in vitro study. Mass spectrometry-proteomics analysis and protein co-immunoprecipitation assays were conducted to dissect the molecular mechanism., Results: CHK1 was downregulated in myocardium post I/R and AMCMs post oxygen-glucose deprivation/re‑oxygenation (OGD/R). In vivo, CHK1 overexpression protected against I/R induced cardiac dysfunction, while heterogenous CHK1 knockout exacerbated cardiomyopathy. In vitro, CHK1 inhibited OGD/R-induced cardiomyocyte apoptosis and bolstered cardiomyocyte survival. Mechanistically, CHK1 attenuated oxidative stress and preserved mitochondrial metabolism in cardiomyocytes under I/R. Moreover, disrupted mitochondrial homeostasis in I/R myocardium was restored by CHK1 through the promotion of mitochondrial biogenesis and mitophagy. Through mass spectrometry analysis following co-immunoprecipitation, SIRT1 was identified as a direct target of CHK1. The 266-390 domain of CHK1 interacted with the 160-583 domain of SIRT1. Importantly, CHK1 phosphorylated SIRT1 at Thr530 residue, thereby inhibiting SMURF2-mediated degradation of SIRT1. The role of CHK1 in maintaining mitochondrial dynamics control and myocardial protection is abolished by SIRT1 inhibition, while inactivated mutation of SIRT1 Thr530 fails to reverse the impaired mitochondrial dynamics following CHK1 knockdown. CHK1 Δ390 amino acids (aa) mutant functioned similarly to full-length CHK1 in scavenging ROS and maintaining mitochondrial dynamics. Consistently, cardiac-specific SIRT1 knockdown attenuated the protective role of CHK1 in I/R injury., Conclusions: Our findings revealed that CHK1 mitigates I/R injury and restores mitochondrial dynamics in cardiomyocytes through a SIRT1-dependent mechanism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The potential of circular RNAs (circRNAs) as biomarkers and therapeutic targets is becoming increasingly evident, yet their roles in cardiac regeneration and myocardial renewal remain largely unexplored. Here, we investigated the function of circIGF1R and related mechanisms in cardiac regeneration. Through analysis of circRNA sequencing data from neonatal and adult cardiomyocytes, circRNAs associated with regeneration were identified. Our data showed that circIGF1R expression was high in neonatal hearts, decreased with postnatal maturation, and up-regulated after cardiac injury. The elevation was validated in patients diagnosed with acute myocardial infarction (MI) within 1 week. In human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and myocardial tissue from mice after apical resection and MI, we observed that circIGF1R overexpression enhanced cardiomyocyte proliferation, reduced apoptosis, and mitigated cardiac dysfunction and fibrosis, while circIGF1R knockdown impeded endogenous cardiac renewal. Mechanistically, we identified circIGF1R binding proteins through circRNA precipitation followed by mass spectrometry. RNA pull-down Western blot and RNA immunoprecipitation demonstrated that circIGF1R directly interacted with DDX5 and augmented its protein level by suppressing ubiquitin-dependent degradation. This subsequently triggered the β-catenin signaling pathway, leading to the transcriptional activation of cyclin D1 and c-Myc. The roles of circIGF1R and DDX5 in cardiac regeneration were further substantiated through site-directed mutagenesis and rescue experiments. In conclusion, our study highlights the pivotal role of circIGF1R in facilitating heart regeneration and repair after ischemic insults. The circIGF1R/DDX5/β-catenin axis emerges as a novel therapeutic target for enhancing myocardial repair after MI, offering promising avenues for the development of regenerative therapies., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Tian-Kai Shan et al.)

Background: Transcranial alternating current stimulation (tACS) can apply currents of varying intensity to the scalp, modulating cortical excitability and brain activity. tACS is a relatively new neuromodulation intervention that is now widely used in clinical practice. Many papers related to tACS have been published in various journals. However, there are no articles that objectively and directly introduce the development trend and research hotspots of tACS. Therefore, the aim of this study is to use CiteSpace to visually analyze the recent tACS-related publications, systematically and in detail summarize the current research hotspots and trends in this field, and provide valuable information for future tACS-related research., Material and Methods: The database Web of Science Core Collection Science Citation Index Expanded was used and searched from build to 4 August 2023. Using the CiteSpace to analyze the authors, institutions, countries, keywords, co-cited authors, journals, and references., Results: A total of 677 papers were obtained. From 2008 to 2023, the number of publications shows an increasing trend, albeit with some fluctuations. The most productive country in this field was Germany. The institution with the highest number of publications is Carl von Ossietzky University of Oldenburg ( n = 50). According to Bradford's law, 7 journals are considered core journals in the field. Herrmann, CS was the author with the most publications ( n = 40), while Antal, A was the author with the highest number of co-citations ( n = 391) and betweenness centrality ( n = 0.16). Disease, neural mechanisms of the brain and electric stimulation are the major research areas in the field. The effect of tACS in different diseases, multi-site stimulation, combined treatment and evaluation are the future research hotspots and trends., Conclusion: tACS has research value and research potential, and more and more researchers are paying attention to it. The findings of this bibliometric study provide the current status and trends in the clinical research of tACS and may help researchers to identify hotspots s and explore new research directions in this field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Shen, Wang, Gong, Zhou, Qian and Tang.)

Patients with caspase-associated recruitment domain-9 (CARD9) deficiency are more likely to develop invasive fungal disease that affect CNS. However, the understanding of how Candida invades and persists in CNS is still limited. We here reported a 24-year-old woman who were previously immunocompetent and diagnosed with CNS candidiasis. A novel autosomal recessive homozygous CARD9 mutation (c.184 + 5G > T) from this patient was identified using whole genomic sequencing. Furthermore, we extensively characterized the impact of this CARD9 mutation on the host immune response in monocytes, neutrophils and CD4 + T cells, using single cell sequencing and in vitro experiments. Decreased pro-inflammatory cytokine productions of CD14 + monocyte, impaired Th17 cell differentiation, and defective neutrophil accumulation in CNS were found in this patient. In conclusion, this study proposed a novel mechanism of CNS candidiasis development. Patients with CNS candidiasis in absence of known immunodeficiencies should be analyzed for CARD9 gene mutation as the cause of invasive fungal infection predisposition., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Milk is an important consumer product with high nutritional value. The presence of veterinary drug residues in milk owing to the indiscriminate use of veterinary drugs may affect consumer health. In the mass spectrometric analysis of trace compounds, chromatographic co-eluting components easily interfere with the mass spectral signals obtained, affecting the accuracy of qualitative and quantitative analyses. Matrix purification is a promising method to reduce the matrix effect. Chitosan is a natural biopolymer with numerous active functional groups such as amino, acetyl, and hydroxyl groups; these groups can adsorb lipids through hydrophobic and electrostatic interactions. Chitosan also has the advantages of low production cost, stable chemical properties, and convenient modification. Novel chitosan-based materials are promising candidates for lipid purification. In this study, a chitosan membrane was modified with trimethoxyoctadecylsilane (C 18 -CSM). C 18 -CSM was prepared through one-step hydrolysis and used as a dispersive solid phase extraction (DSPE) adsorbent to purify the matrix during milk pretreatment. We combined C 18 -CSM with ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry (UHPLC-Q/Exactive Orbitrap MS) to develop an effective method for the extraction and determination of ofloxacin, enrofloxacin, ciprofloxacin, diazepam, and metronidazole in milk. C 18 -CSM was characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, and water contact angle testing. The results indicated that the material has a rough surface and uniformly dense cross-section. The water contact angle of C 18 -CSM was 104°, indicating its good hydrophobicity. The pretreatment conditions (extraction solvent, dosage of NaCl, extraction frequency, and dosage of C 18 -CSM) that influenced the recoveries of the five veterinary drugs were investigated in detail. The optimal conditions were established as follows: 5% formic acid in acetonitrile, 1 g NaCl, extraction 1 time, 20 mg C 18 -CSM. Separation was performed on a Hypersil GOLD VANQUISH column (100 mm×2.1 mm, 1.9 μm). The mobile phase consisted of 0.1% formic acid aqueous solution and 0.1% formic acid in acetonitrile, and was flowed at a rate of 0.3 mL/min. The sample injection volume was 1 μL, and the column temperature was maintained at 25 ℃. Mass spectrometric analysis was performed in positive electrospray ionization mode. To verify the necessity of the purification material, the matrix effect was investigated using the matrix-matched standard curve method. The use of C 18 -CSM reduced the matrix effects of the five necessity drugs from the range of -22%-8.8% to the range of -13%-3.6%, indicating that C 18 -CSM is a highly efficient DSPE material. Under optimal conditions, the developed method showed good linearities within the range of 0.5-100 μg/L, with correlation coefficients ( r 2 )≥0.9970. The limits of detection(LODs) and quantification (LOQs) were 0.2 μg/L and 0.5 μg/L, respectively. To assess the accuracy and precision of the method, we prepared milk samples with three spiked levels (low, medium, and high). The recoveries of the five veterinary drugs were ranged from 79.5% to 115%, and the intra-day and inter-day relative standard deviations were 7.0%-13% ( n =6) and 1.3%-11% ( n =3), respectively. This study provides a simple, accurate, and reliable method for the rapid and simultaneous determination of the five veterinary drug residues in milk.

Background: Parkinson's disease (PD) is a prevalent neurodegenerative disorder affecting millions globally. It encompasses both motor and non-motor symptoms, with a notable impact on patients' quality of life. Electroencephalogram (EEG) is a non-invasive tool that is increasingly utilized to investigate neural mechanisms in PD, identify early diagnostic markers, and assess therapeutic responses., Methods: The data were sourced from the Science Citation Index Expanded within the Web of Science Core Collection database, focusing on publications related to EEG research in PD from 2004 to 2023. A comprehensive bibliometric analysis was conducted using CiteSpace and VOSviewer software. The analysis began with an evaluation of the selected publications, identifying leading countries, institutions, authors, and journals, as well as co-cited references, to summarize the current state of EEG research in PD. Keywords are employed to identify research topics that are currently of interest in this field through the analysis of high-frequency keyword co-occurrence and cluster analysis. Finally, burst keywords were identified to uncover emerging trends and research frontiers in the field, highlighting shifts in interest and identifying future research directions., Results: A total of 1,559 publications on EEG research in PD were identified. The United States, Germany, and England have made notable contributions to the field. The University of London is the leading institution in terms of publication output, with the University of California closely following. The most prolific authors are Brown P, Fuhr P, and Stam C In terms of total citations and per-article citations, Stam C has the highest number of citations, while Brown P has the highest H-index. In terms of the total number of publications, Clinical Neurophysiology is the leading journal, while Brain is the most highly cited. The most frequently cited articles pertain to software toolboxes for EEG analysis, neural oscillations, and PD pathophysiology. Through analyzing the keywords, four research hotspots were identified: research on the neural oscillations and connectivity, research on the innovations in EEG Analysis, impact of therapies on EEG, and research on cognitive and emotional assessments., Conclusion: This bibliometric analysis demonstrates a growing global interest in EEG research in PD. The investigation of neural oscillations and connectivity remains a primary focus of research. The application of machine learning, deep learning, and task analysis techniques offers promising avenues for future research in EEG and PD, suggesting the potential for advancements in this field. This study offers valuable insights into the major research trends, influential contributors, and evolving themes in this field, providing a roadmap for future exploration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liao, Gao, Qian, Zhou, Li, Gong and Ye.)

Background: The regenerative capacity of the adult mammalian hearts is limited. Numerous studies have explored mechanisms of adult cardiomyocyte cell-cycle withdrawal. This translational study evaluated the effects and underlying mechanism of rhCHK1 (recombinant human checkpoint kinase 1) on the survival and proliferation of cardiomyocyte and myocardial repair after ischemia/reperfusion injury in swine., Methods and Results: Intramyocardial injection of rhCHK1 protein (1 mg/kg) encapsulated in hydrogel stimulated cardiomyocyte proliferation and reduced cardiac inflammation response at 3 days after ischemia/reperfusion injury, improved cardiac function and attenuated ventricular remodeling, and reduced the infarct area at 28 days after ischemia/reperfusion injury. Mechanistically, multiomics sequencing analysis demonstrated enrichment of glycolysis and mTOR (mammalian target of rapamycin) pathways after rhCHK1 treatment. Co-Immunoprecipitation (Co-IP) experiments and protein docking prediction showed that CHK1 (checkpoint kinase 1) directly bound to and activated the Serine 37 (S37) and Tyrosine 105 (Y105) sites of PKM2 (pyruvate kinase isoform M2) to promote metabolic reprogramming. We further constructed plasmids that knocked out different CHK1 and PKM2 amino acid domains and transfected them into Human Embryonic Kidney 293T (HEK293T) cells for CO-IP experiments. Results showed that the 1-265 domain of CHK1 directly binds to the 157-400 amino acids of PKM2. Furthermore, hiPSC-CM (human iPS cell-derived cardiomyocyte) in vitro and in vivo experiments both demonstrated that CHK1 stimulated cardiomyocytes renewal and cardiac repair by activating PKM2 C-domain-mediated cardiac metabolic reprogramming., Conclusions: This study demonstrates that the 1-265 amino acid domain of CHK1 binds to the 157-400 domain of PKM2 and activates PKM2-mediated metabolic reprogramming to promote cardiomyocyte proliferation and myocardial repair after ischemia/reperfusion injury in adult pigs.

Background: Brachial plexus injury is recognized as one of the most severe clinical challenges due to the complex anatomical configuration of the brachial plexus and its propensity for variation, which complicates safe clinical interventions. This study aimed to ascertain the prevalence and characterize the types of brachial plexus variations, and to elucidate their clinical implications., Materials and Methods: We conducted meticulous dissections of 60 formalin-fixed cadavers' upper arm, axilla and lower neck to reveal and assess the roots, trunks, divisions, cords, and branches of the brachial plexus. The pattern of branching was noted by groups of dissecting medical students and confirmed by the senior anatomists. The variations discovered were record and photographed using a digital camera for further analysis., Results: Variations in the brachial plexus were identified in 40 of the 60 cadavers, yielding a prevalence rate of 66.7%. These variations were classified into root anomalies (2.1%), trunk anomalies (8.5%), division anomalies (2.1%), and cord anomalies (4.3%). Notably, anomalies in communicating branches were observed in 39 cadavers (83.0%): 14 with bilateral anomalies, 14 with anomalies on the left side, and 11 on the right side. These communicating branches formed connections between the roots and other segments, including trunks, cords, and terminal nerves, and involved the median, musculocutaneous, and ulnar nerves., Conclusion: The frequency and diversity of brachial plexus variations, particularly in communicating branches, are significant in cadavers. It is imperative that these variations are carefully considered during the diagnostic process, treatment planning, and prior to procedures such as supraclavicular brachial plexus blocks and nerve transfers, to mitigate the risk of iatrogenic complications., (© 2024 The Author(s). Microsurgery published by Wiley Periodicals LLC.)

The peroxisome is a versatile organelle that performs diverse metabolic functions. PEX3, a critical regulator of the peroxisome, participates in various biological processes associated with the peroxisome. Whether PEX3 is involved in peroxisome-related redox homeostasis and myocardial regenerative repair remains elusive. We investigate that cardiomyocyte-specific PEX3 knockout (Pex3-KO) results in an imbalance of redox homeostasis and disrupts the endogenous proliferation/development at different times and spatial locations. Using Pex3-KO mice and myocardium-targeted intervention approaches, the effects of PEX3 on myocardial regenerative repair during both physiological and pathological stages are explored. Mechanistically, lipid metabolomics reveals that PEX3 promotes myocardial regenerative repair by affecting plasmalogen metabolism. Further, we find that PEX3-regulated plasmalogen activates the AKT/GSK3β signaling pathway via the plasma membrane localization of ITGB3. Our study indicates that PEX3 may represent a novel therapeutic target for myocardial regenerative repair following injury., (© 2024. The Author(s).)

Aim: To investigate botulinum toxin A (BTXA) efficacy on small-angle (≤25 Δ ) acute acquired concomitant esotropia (AACE) in early-stage patients., Methods: The electronic medical record data of AACE patients during March 2019 and June 2023 were collected in this retrospective and hospital-based cohort study. A total of 72 small-angle AACE patients received BTXA extraocular muscle injection. Patients were grouped by onset-to-treatment time (Group A: ≤6mo, Group B: >6mo). Deviation of esotropia, eye alignment and stereopsis were analyzed at the period of pre/post-injection (1wk, 1, 3, and 6mo). Orthophoria rate at 6mo (horizontal deviation <10 Δ and binocular single vision) were considered as outcome index., Results: There were no significant baseline differences ( P >0.05) between two groups except onset-to-treatment time (2mo vs 11mo, P <0.001). Higher orthophoria rates were in Group A at last follow-up (94.74% vs 73.53%, P =0.013). Post-BTXA deviations of two groups at 1mo showed no difference ( P >0.05); while in 3 and 6mo Group A was significantly smaller than group B (all P <0.001). No statistically significant differences were observed among all post-BTXA deviations of near and distance in Group A. In Group B, deviation at 3mo (near: 2 Δ vs 0, P <0.001; distance: 4 Δ vs 0, P <0.001) and 6mo (near: 6 Δ vs 0, P <0.001; distance: 6 Δ vs 0, P <0.001) was significant increased compared to deviation at 1wk after treatment. Group A showed better stereopsis recovery in last follow-up compared to Group B (80″ vs 200″, P =0.002). Both groups obtained improved stereopsis after treatment (Group A: 80″ vs 300″, P <0.001; Group B: 200″ vs 300″, P =0.037)., Conclusion: BTXA is effective for AACE with small deviation (≤25 Δ ) in early stage. Delayed treatment (>6mo) may reduce BTXA efficacy. Early BTXA intervention benefits long-term eye alignment and stereopsis recovery., Competing Interests: Conflicts of Interest: Ma RT, None; Hu DWJ, None; Zhou LH, None; Li WP, None; Li YJ, None; Yi BX, None., (International Journal of Ophthalmology Press.)

Abscisic acid (ABA) plays a crucial role in promoting plant stress resistance and seed dormancy. However, how ABA regulates rice quality remains unclear. This study identifies a key transcription factor SLR1-like2 (SLRL2), which mediates the ABA-regulated amylose content (AC) of rice. Mechanistically, SLRL2 interacts with NF-YB1 to co-regulate Wx, a determinant of AC and rice quality. In contrast to SLR1, SLRL2 is ABA inducible but insensitive to GA. In addition, SLRL2 exhibits DNA-binding activity and directly regulates the expression of Wx, bHLH144 and MFT2. SLRL2 competes with NF-YC12 for interaction with NF-YB1. NF-YB1 also directly represses SLRL2 transcription. Genetic validation supports that SLRL2 functions downstream of NF-YB1 and bHLH144 in regulating rice AC. Thus, an NF-YB1-SLRL2-bHLH144 regulatory module is successfully revealed. Furthermore, SLRL2 regulates rice dormancy by modulating the expression of MFT2. In conclusion, this study revealed an ABA-responsive regulatory cascade that functions in both rice quality and seed dormancy., (© 2024. The Author(s).)

Soil microbes are key drivers in regulating the phosphorus cycle. Elucidating the microbial mineralization process of soil phosphorus-solubilizing bacteria is of great significance for improving nutrient uptake and yield of crops. This study investigated the mechanism by which citrus cultivation affects the soil microbial acquisition strategy for phosphorus by measuring the abundance of the phoD gene, microbial community diversity and structure, and soil phosphorus fractions in the soils of citrus orchards and adjacent natural forests. The results showed that citrus cultivation could lead to a decrease in soil pH and an accumulation of available phosphorus in the soil, with a content as high as 112 mg·kg -1 , which was significantly higher than that of natural forests (3.7 mg·kg -1 ). Citrus cultivation also affected the soil phosphorus fractions, with citrus soil having higher levels of soluble phosphorus (CaCl 2 -P), citrate-extractable phosphorus (Citrate-P), and mineral-bound phosphorus (HCl-P). The phosphorus fractions of natural forest soils were significantly lower than those of citrus soils, whereas the phoD gene abundance and alkaline phosphatase activity were significantly higher in natural forest soils than in citrus soils. High-throughput sequencing results showed that the Shannon diversity index of phosphate-solubilizing bacteria in citrus soils was 4.61, which was significantly lower than that of natural forests (5.35). The microbial community structure in natural forests was also different from that of citrus soils. In addition, the microbial community composition of phosphate-solubilizing bacteria in citrus soils was also different from that of natural forests, with the relative abundance of Proteobacteria being lower in natural forest soils than in citrus soils. Therefore, citrus cultivation led to a shift of soil microbial acquisition strategy for phosphorus, with external phosphorus addition being the main strategy in citrus soils, whereas microbial mineralization of organic phosphorus was the main strategy in natural forest soils to meet their growth requirements.

Objectives: To explore the seroprevalence of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies in non-HIV cryptococcal meningitis (CM) and assess its predictive value for survival., Methods: This is a retrospective study of 12 years of non-HIV CM. We detected serum anti-GM-CSF autoantibodies, and evaluated the clinical features and outcomes, together with the exploration of prognostic factors for 2-week and 1-year survival., Results: A total of 584 non-HIV CM cases were included. 301 of 584 patients (51.5%) were phenotypically healthy. 264 Cryptococcus isolates were obtained from cerebrospinal fluid (CSF) culture, of which 251 were identified as C. neoformans species complex and 13 as C. gattii species complex. Thirty-seven of 455 patients (8.1%) tested positive for serum anti-GM-CSF autoantibodies. Patients with anti-GM-CSF autoantibodies were more susceptible to C. gattii species complex infection (66.7% vs. 6.3%; p < 0.001) and more likely to develop pulmonary mass lesions with a diameter >3 centimetres (42.9% vs. 6.5%; p 0.001). Of 584 patients 16 (2.7%) died within 2 weeks, 77 of 563 patients (13.7%) died at 1 year, and 93 of 486 patients (19.1%) lived with disabilities at 1 year. Univariant Cox regression analysis found that anti-GM-CSF autoantibodies were associated with lower 1-year survival (HR, 2.66; 95% CI, 1.34-5.27; p 0.005). Multivariable Cox proportional hazards modelling revealed that CSF cryptococcal antigen titres ≥1:1280 were associated with both, reduced 2-week and 1-year survival rates (HR, 5.44; 95% CI, 1.23-24.10; p 0.026 and HR, 5.09; 95% CI, 1.95-13.26; p 0.001)., Discussion: Presence of serum anti-GM-CSF autoantibodies is predictive of poor outcomes, regardless of host immune status and the causative Cryptococcus species complex., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Preoperative frailty and surgical waiting times are associated with the occurrence of adverse outcomes in patients with hip fractures. Specifically, we aimed to investigate the influence of frailty status and surgical timing on the risk of serious adverse events during hospitalization., Methods: This study utilized an observational single cohort design and included patients aged ≥60 years with a primary diagnosis of hip fracture. Frailty was assessed using the chart-derived frailty index (CFI), which was calculated based on demographic and routine laboratory variables. The primary outcome of interest was the occurrence of in-hospital serious adverse events. A multivariate logistic regression model was utilized to examine the risk factors influencing outcomes., Results: The study included 427 participants, with a mean age of 80.28 ± 8.13 years and 64.2% of whom were female. Patients with high CFI have more comorbidities ( P < .001), lower surgical rates ( P = .002), and delayed surgical times ( P = .033). A total of 239 patients (56.0%) experienced serious adverse events. The high CFI group had a significantly higher occurrence of serious adverse events compared to the low CFI group (73.4% vs 48.5%, P < .001). After adjusting for surgical timing and covariates, the multivariate logistic regression analysis revealed that high frailty significantly increased the risk for serious adverse events (OR = 2.47, 95% CI 1.398-4.412), infection (OR = 1.99, 95% CI 1.146-3.446), acute heart failure (OR = 3.37, 95% CI 1.607-7.045). However, the timing of surgery did not demonstrate any association with these outcomes. In addition, after adjusting for surgical factors, high CFI remains an independent risk factor for these complications., Conclusions: Frailty serves as a reliable predictor of the probability of encountering severe adverse events while hospitalized for elderly individuals with hip fractures. This method has the potential to pinpoint particular modifiable factors that necessitate intervention, whereas the impact of surgical timing remains uncertain and necessitates additional research., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: The beet armyworm, Spodoptera exigua (Hübner), is an important agricultural pest worldwide that has caused serious economic losses in the main crop-producing areas of China. To effectively monitor and control this pest, it is crucial to investigate its population dynamics and seasonal migration patterns in northern China., Methods: In this study, we monitored the population dynamics of S. exigua using sex pheromone traps in Shenyang, Liaoning Province from 2012 to 2022, combining these data with amigration trajectory simulation approach and synoptic weather analysis., Results: There were significant interannual and seasonal variations in the capture number of S. exigua, and the total number of S. exigua exceeded 2,000 individuals in 2018 and 2020. The highest and lowest numbers of S. exigua were trapped in September and May, accounting for 34.65% ± 6.81% and 0.11% ± 0.04% of the annual totals, respectively. The average occurrence period was 140.9 ± 9.34 days during 2012-2022. In addition, the biomass of S. exigua also increased significantly during these years. The simulated seasonal migration trajectories also revealed varying source regions in different months, primarily originated from Northeast China and East China. These unique insights into the migration patterns of S. exigua will contribute to a deeper understanding of its occurrence in northern China and provide a theoretical basis for regional monitoring, early warning, and the development of effective management strategies for long-range migratory pests., Competing Interests: The authors declare there are no competing interests., (©2024 Ma et al.)

Background: Vesicular stomatitis virus (VSV), a vector-borne pathogen of livestock, emerges periodically in the western US. In New Mexico (NM), US, most cases occur close to the Rio Grande River, implicating black flies (Simulium spp.) as a possible vector. In 2020, VS cases were reported in NM from April to May, although total black fly abundance remained high until September. We investigated the hypothesis that transience of local VSV transmission results from transient abundance of key, competent black fly species. Additionally, we investigated whether irrigation canals in southern NM support a different community of black flies than the main river. Lastly, to gain insight into the source of local black flies, in 2023 we collected black fly larvae prior to the release of water into the Rio Grande River channel., Methods: We randomly sub-sampled adult black flies collected along the Rio Grande during and after the 2020 VSV outbreak. We also collected black fly adults along the river in 2021 and 2022 and at southern NM farms and irrigation canals in 2022. Black fly larvae were collected from dams in the area in 2023. All collections were counted, and individual specimens were subjected to molecular barcoding for species identification., Results: DNA barcoding of adult black flies detected four species in 2020: Simulium meridionale (N = 158), S. mediovittatum (N = 83), S. robynae (N = 26) and S. griseum/notatum (N = 1). Simulium robynae was only detected during the VSV outbreak period, S. meridionale showed higher relative abundance, but lower absolute abundance, during the outbreak than post-outbreak period, and S. mediovittatum was rare during the outbreak period but predominated later in the summer. In 2022, relative abundance of black fly species did not differ significantly between the Rio Grande sites and farm and irrigation canals. Intriguingly, 63 larval black flies comprised 56% Simulium vittatum, 43% S. argus and 1% S. encisoi species that were either extremely rare or not detected in previous adult collections., Conclusions: Our results suggest that S. robynae and S. meridionale could be shaping patterns of VSV transmission in southern NM. Thus, field studies of the source of these species as well as vector competence studies are warranted., (© 2024. The Author(s).)

Background: Emerging diagnostic modalities suggest that miRNA profiles within extracellular vesicles (EVs) isolated from peripheral blood specimens may provide a non-invasive diagnostic alternative for dementia and neurodegenerative disorders. Given that EVs confer a protective environment against miRNA enzymatic degradation, the miRNAs enriched in the EV fraction of blood samples could serve as more stable and clinically relevant biomarkers compared to those obtained from serum., Objective: To compare miRNAs isolated from EVs versus serum in blood taken from Alzheimer's disease (AD) dementia patients and control cohorts., Methods: We compared 25 AD patients to 34 individuals who exhibited no cognitive impairments (NCI). Subjects were Singapore residents with Chinese heritage. miRNAs purified from serum versus blood-derived EVs were analyzed for associations with AD dementia and medial temporal atrophy detected by magnetic resonance imaging., Results: Compared to serum-miRNAs, we identified almost twice as many EV-miRNAs associated with AD dementia, and they also correlated more significantly with medial temporal atrophy, a neuroimaging marker of AD-brain pathology. We further developed combination panels of serum-miRNAs and EV-miRNAs with improved performance in identifying AD dementia. Dominant in both panels was miRNA-1290., Conclusions: This data indicates that miRNA profiling from EVs offers diagnostic superiority. This underscores the role of EVs as vectors harboring prognostic biomarkers for neurodegenerative disorders and suggests their potential in yielding novel biomarkers for AD diagnosis.

Administration of CHK1-targeted anticancer therapies is associated with an increased cumulative risk of cardiac complications, which is further amplified when combined with gemcitabine. However, the underlying mechanisms remain elusive. In this study, we generated hiPSC-CMs and murine models to elucidate the mechanisms underlying CHK1 inhibition combined with gemcitabine-induced cardiotoxicity and identify potential targets for cardioprotection. Mice were intraperitoneally injected with 25 mg/kg CHK1 inhibitor AZD7762 and 20 mg/kg gemcitabine for 3 weeks. hiPSC-CMs and NMCMs were incubated with 0.5 uM AZD7762 and 0.1 uM gemcitabine for 24 h. Both pharmacological inhibition or genetic deletion of CHK1 and administration of gemcitabine induced mtROS overproduction and pyroptosis in cardiomyocytes by disrupting mitochondrial respiration, ultimately causing heart atrophy and cardiac dysfunction in mice. These toxic effects were further exacerbated with combination administration. Using mitochondria-targeting sequence-directed vectors to overexpress CHK1 in cardiomyocyte (CM) mitochondria, we identified the localization of CHK1 in CM mitochondria and its crucial role in maintaining mitochondrial redox homeostasis for the first time. Mitochondrial CHK1 function loss mediated the cardiotoxicity induced by AZD7762 and CHK1-knockout. Mechanistically, mitochondrial CHK1 directly phosphorylates SIRT3 and promotes its expression within mitochondria. On the contrary, both AZD7762 or CHK1-knockout and gemcitabine decreased mitochondrial SIRT3 abundance, thus resulting in respiration dysfunction. Further hiPSC-CMs and mice experiments demonstrated that SIRT3 overexpression maintained mitochondrial function while alleviating CM pyroptosis, and thereby improving mice cardiac function. In summary, our results suggest that targeting SIRT3 could represent a novel therapeutic approach for clinical prevention and treatment of cardiotoxicity induced by CHK1 inhibition and gemcitabine., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To explore the prognostic value of circulating tumor DNA (ctDNA) testing in patients with refractory/relapsed diffuse large B-cell lymphoma (R/R DLBCL) undergoing chimeric antigen receptor T-cell (CAR-T) therapy, and to guide the prevention and subsequent treatment of CAR-T-cell therapy failure. Methods: In this study, 48 patients with R/R DLBCL who received CAR-T-cell therapy at the First Affiliated Hospital of Zhejiang University School of Medicine between December 2017 and March 2022 were included. Furthermore, ctDNA testing of 187 lymphoma-related gene sets was performed on peripheral blood samples obtained before treatment. The patients were divided into complete remission and noncomplete remission groups. The chi-square test and t -test were used to compare group differences, and the Log-rank test was used to compare the differences in survival. Results: Among the patients who did not achieve complete remission after CAR-T-cell therapy for R/R DLBCL, the top ten genes with the highest mutation frequencies were TP53 (41%), TTN (36%), BCR (27%), KMT2D (27%), IGLL5 (23%), KMT2C (23%), MYD88 (23%), BTG2 (18%), MUC16 (18%), and SGK1 (18%). Kaplan-Meier survival analysis revealed that patients with ctDNA mutation genes >10 had poorer overall survival (OS) rate (1-year OS rate: 0 vs 73.8%, P <0.001) and progression-free survival (PFS) rate (1-year PFS rate: 0 vs 51.8%, P =0.011) compared with patients with ctDNA mutation genes ≤10. Moreover, patients with MUC16 mutation positivity before treatment had better OS (2-year OS rate: 56.8% vs 26.7%, P =0.046), whereas patients with BTG2 mutation positivity had poorer OS (1-year OS rate: 0 vs 72.5%, P =0.005) . Conclusion: ctDNA detection can serve as a tool for evaluating the efficacy of CAR-T-cell therapy in patients with R/R DLBCL. The pretreatment gene mutation burden, mutations in MUC16 and BTG2 have potential prognostic value.

Propose: Registered nurses (RNs) are considered to be a major source of professional supportive care for women diagnosed with gynecological cancer (GC). This study described the level of perceived professional benefits and explored association between perceived professional benefits, sense of coherence (SOC), and coping strategies in Chinese RNs caring for women diagnosed with GC., Method: A cross-sectional survey was employed to collect data using the Nurses' Perceived Professional Benefits Questionnaire (NPPBQ), Sense of coherence scale (SOC-13), and Brief Coping Orientation to Problems Experienced (Brief COPE). The questionnaires were administered to 250 RNs in China. The correlations between NPPBQ, SOC-13, and Brief COPE were evaluated with Pearson's correlation coefficient. Multiple regression analysis was performed to assess the relative contribution of each possible factor in explaining variance in the increased NPPBQ., Results: The total score for the NPPBQ was 142.4 (range 33.0-165.0). SOC, dysfunctional coping strategies, and problem-focused coping strategies were recognized as predictors of RNs' perceived professional benefit, while, emotion-focused coping strategies were not significantly associated with RNs' perceived professional benefits., Conclusions: The findings indicate that RNs who have high levels of SOC, dysfunctional coping strategies, and problem-focused coping strategies tend to experience more perceived professional benefit. These findings propose new perspectives for nursing managers to promote RNs' perceived professional benefit by helping RNs to find meaningfulness when caring for women diagnosed with GC, increasing RNs' communication skills to improve their relationship with patients, and training RNs to use coping strategies effectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The role of lysophosphatidic acid (LPA) signaling in psychiatric disorders and drug abuse is significant. LPA receptors are widely expressed in the central nervous system, including the lateral habenula (LHb). Recent studies suggest that LHb is involved in a negative emotional state during alcohol withdrawal, which can lead to relapse. The current study examines the role of LHb LPA signaling in the negative affective state associated with alcohol withdrawal. Adult male Long-Evans rats were trained to consume either alcohol or water for eight weeks. At 48 h of withdrawal, alcohol-drinking rats showed anxiety- and depression-like symptoms, along with a significant increase in LPA signaling and related neuronal activation molecules, including autotaxin (ATX, Enpp2), LPA receptor 1/3 (LPA1/3), βCaMKII, and c-Fos. However, there was a decrease in lipid phosphate phosphatase-related protein type 4 (LPPR4) in the LHb. Intra-LHb infusion of the LPA1/3 receptor antagonist ki-16425 or PKC-γ inhibitor Go-6983 reduced the abnormal behaviors and elevated relapse-like ethanol drinking. It also normalized high LPA1/3 receptors and enhanced AMPA GluA1 phosphorylation in Ser831 and GluA1/GluA2 ratio. Conversely, selective activation of LPA1/3 receptors by intra-LHb infusion of 18:1 LPA induced negative affective states and upregulated βCaMKII-AMPA receptor phosphorylation in Naive rats, which were reversed by pretreatment with intra-LHb Go-6983. Our findings suggest that disturbances in LPA signaling contribute to adverse affective disorders during alcohol withdrawal, likely through PKC-γ/βCaMKII-linked glutamate signaling. Targeting LPA may therefore be beneficial for individuals suffering from alcohol use disorders., (© 2023. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Chronic pulmonary aspergillosis (CPA) is a chronic and progressive fungal disease with high morbidity and mortality. Avoiding diagnostic delay and misdiagnosis are concerns for CPA patients. However, diagnostic practice is poorly evaluated, especially in resource-constrained areas where Aspergillus antibody testing tools are lacking. This study aimed to investigate the diagnostic laboratory findings in a retrospective CPA cohort and to evaluate the performance of a novel Aspergillus IgG lateral flow assay (LFA; Era Biology, Tianjin, China). During January 2016 and December 2021, suspected CPA patients were screened at the Center for Infectious Diseases at Huashan Hospital. A total of 126 CPA patients were enrolled. Aspergillus IgG was positive in 72.1% with chronic cavitary pulmonary aspergillosis, 75.0% with chronic necrotizing pulmonary aspergillosis, 41.7% with simple aspergilloma, and 30.3% with Aspergillus nodule(s). The cavitary CPA subtypes had significantly higher levels of Aspergillus IgG. Aspergillus IgG was negative in 52 patients, who were finally diagnosed by histopathology, respiratory culture, and metagenomic next-generation sequencing (mNGS). Sputum culture was positive in 39.3% (42/107) of patients and Aspergillus fumigatus was the most common species (69.0%, 29/42). For CPA cohort versus controls, the sensitivity and specificity of the LFA were 55.6% and 92.7%, respectively. In a subgroup analysis, the LFA was highly sensitive for A. fumigatus-associated chronic cavitary pulmonary aspergillosis (CCPA; 96.2%, 26/27). Given the complexity of the disease, a combination of serological and non-serological tests should be considered to avoid misdiagnosis of CPA. The novel LFA has a satisfactory performance and allows earlier screening and diagnosis of CPA patients. IMPORTANCE There are concerns on avoiding diagnostic delay and misdiagnosis for chronic pulmonary aspergillosis due to its high morbidity and mortality. A proportion of CPA patients test negative for Aspergillus IgG. An optimal diagnostic strategy for CPA requires in-depth investigation based on real-world diagnostic practice, which has been rarely discussed. We summarized the clinical and diagnostic laboratory findings of 126 CPA patients with various CPA subtypes. Aspergillus IgG was the most sensitive test for diagnosing CPA. However, it was negative in 52 patients, who were finally diagnosed by non-serological tests, including biopsy, respiratory culture, and metagenomic next-generation sequencing. We also evaluated a novel Aspergillus IgG lateral flow assay, which showed a satisfactory performance in cavitary CPA patients and was highly specific to Aspergillus fumigatus. This study gives a full picture of the diagnostic practice for CPA patients in Chinese context and calls for early diagnosis of CPA with combined approaches., Competing Interests: The authors declare no conflict of interest.

Recent studies have demonstrated that ovarian granular cells (OGCs) pyroptosis is present in the ovaries of polycystic ovary syndrome (PCOS) mice and that NLRP3 activation destroys follicular functions. Metformin has been shown to protect against PCOS by reducing insulin resistance in women, whereas its role in OGC pyroptosis is unknown. This study aimed to investigate the impact of metformin on OGC pyroptosis and the underlying mechanisms. The results showed that treating a human granulosa-like tumor cell line (KGN) with metformin significantly decreased LPS-induced expression of miR-670-3p, NOX2, NLRP3, ASC, cleaved caspase-1, and GSDMD-N. Cellular caspase-1 activity; ROS production; oxidative stress; and the secretion of IL-1β, IL-6, IL-18, and TNF-α were also diminished. These effects were amplified by adding N-acetyl-L-cysteine (NAC), a pharmacological inhibitor of ROS. In contrast, metformin's anti-pyroptosis and anti-inflammatory effects were robustly ameliorated by NOX2 overexpression in KGN cells. Moreover, bioinformatic analyses, RT-PCR, and Western blotting showed that miR-670-3p could directly bind to the NOX2 (encoded by the CYBB gene in humans) 3'UTR and decrease NOX2 expression. Metformin-induced suppression of NOX2 expression, ROS production, oxidative stress, and pyroptosis was significantly alleviated by transfection with the miR-670-3p inhibitor. These findings suggest that metformin inhibits KGN cell pyroptosis via the miR-670-3p/NOX2/ROS pathway.

Background: Central nervous system (CNS) aspergillosis is an uncommon but fatal disease, the diagnosis of which is still difficult., Objectives: We aim to explore the diagnositic performance of noncultural methods for CNS aspergillosis., Methods: In this retrospective study, all pathologically confirmed rhinosinusitis patients in whom cerebrospinal fluid (CSF) galactomannan (GM) test and metagenomic next-generation sequencing (mNGS) had been performed were included. We evaluated the diagnostic performances of CSF GM optical density indexes (ODI) at different cut-off values and compared performance with mNGS in patients with and without CNS aspergillosis, as well as in patients with different manifestations of CNS aspergillosis., Results: Of the 21 proven and probable cases, one had positive culture result, five had positive mNGS results and 10 had a CSF GM ODI of >0.7. Sample concordance between mNGS and GM test was poor, but best diagnostic performance was achieved by combination of GM test (ODI of >0.7) and mNGS, which generated a sensitivity of 61.9% and specificity of 82.6%. Further investigation of combination diagnostic performances in different kind of CNS aspergillosis was also conducted. Lowest sensitivity (42.9%) was identified in abscess group, while increased sensitivity (60.0%) was achieved in abscess with encephalitis groups. Combination test exhibited the best performance for encephalitis patients who had only CSF abnormalities, in whom the sensitivity and specificity were 77.8% and 82.6%, respectively., Conclusions: In conclusion, combination of these two tests might be useful for diagnosis of CNS aspergillosis associated with fungal rhinosinusitis, especially in encephalitis patients., (© 2022 The Authors. Mycoses published by Wiley-VCH GmbH.)

Aim: To observe the surgical effects of slanted bilateral lateral recession (S-BLR) versus conventional bilateral lateral recession (C-BLR) in convergence insufficiency intermittent exotropia (CI-IXT)., Methods: Using a randomized, double-blind, prospective design, 22 patients with CI-IXT who were admitted to Renmin Hospital of Wuhan University from July 2019 to December 2020 were included. Patients were randomly divided into either S-BLR or C-BLR group for their subsequent strabismus surgery. All patients were followed up for 12mo. Near deviation, distant deviation, and near-distance difference (NDD) were measured in all patients., Results: Twelve months after surgery, NDD improvement was 10 (8, 13) prismatic degrees (PD) in S-BLR group and 3 (1, 6) PD in C-BLR group ( P =0.011). The near deviation of S-BLR group was 0 (-2, 2) PD, while that of C-BLR group was -4 (-6, -3) PD ( P =0.005). Before and after surgery, the difference in the distant deviation between the two groups was not statistically significant. There was no statistically significant difference in near stereopsis between the two groups ( P =0.380) at 12mo. The success rate at 12mo after operation was 90.91% and 72.73% in the two groups ( P =0.280)., Conclusion: CI-IXT patients treated with S-BLR have better surgical outcomes than those treated with C-BLR, which indicates S-BLR is a safe and effective operation pattern., (International Journal of Ophthalmology Press.)

Background: Cryptococcal meningitis (CM) is increasingly recognised in human immunodeficiency virus (HIV)-uninfected patients with high mortality. The efficacy and safety profiles of induction therapy with high-dose fluconazole plus flucytosine remain unclear., Methods: HIV-uninfected CM patients who received high-dose fluconazole (800 mg/d) for initial therapy in Huashan Hospital were included in this retrospective study from January 2013 to December 2018. Efficacy and safety of initial therapy, clinical outcomes and risk factors were evaluated., Results: Twenty-seven (71.1%) patients who received high-dose fluconazole with flucytosine combination therapy and 11 (28.9%) having fluconazole alone for induction therapy were included. With a median duration of 42 days (IQR, 28-86), the successful response rate of initial therapy was 76.3% (29/38), while adverse drug reactions occurred in 14 patients (36.8%). The rate of persistently positive cerebrospinal fluid (CSF) culture results was 30.6% at 2 weeks, which was significantly associated with CSF CrAg titre >1:1280 (OR 9.56; 95% CI 1.40-103.65; p = .010) and CSF culture of Cryptococcus >3.9 log 10 CFU/ml (OR 19.20; 95% CI 1.60-920.54; p = .011), and decreased to 8.6% at 4 weeks. One-year mortality was 15.8% (6/38), and low serum albumin (35 g/L) was found as an independent risk factor for 1-year mortality (HR 6.31; 95% CI 1.150-34.632; p = .034)., Conclusions: Induction therapy with high-dose fluconazole (800 mg/d), combined with flucytosine, effectively treated HIV-uninfected CM and was well tolerated. Long-term fluconazole treatment with continued monitoring is beneficial for patients with persistent infection., (© 2022 The Authors. Mycoses published by Wiley-VCH GmbH.)

Previous studies in Arabidopsis reported that the PPR protein SOAR1 plays critical roles in plant response to salt stress. In this study, we reported that expression of the Arabidopsis SOAR1 (AtSOAR1) in rice significantly enhanced salt tolerance at seedling growth stage and promoted grain productivity under salt stress without affecting plant productivity under non-stressful conditions. The transgenic rice lines expressing AtSOAR1 exhibited increased ABA sensitivity in ABA-induced inhibition of seedling growth, and showed altered transcription and splicing of numerous genes associated with salt stress, which may explain salt tolerance of the transgenic plants. Further, we overexpressed the homologous gene of SOAR1 in rice, OsSOAR1, and showed that transgenic plants overexpressing OsSOAR1 enhanced salt tolerance at seedling growth stage. Five salt- and other abiotic stress-induced SOAR1-like PPRs were also identified. These data showed that the SOAR1-like PPR proteins are positively involved in plant response to salt stress and may be used for crop improvement in rice under salinity conditions through transgenic manipulation., (© 2022. The Author(s).)

Aim: To investigate the effects of micro-injection of botulinum toxin A (BTXA) on acute acquired comitant esotropia (AACE)., Methods: A total of 33 AACE patients who underwent BTXA micro-injection at Renmin Hospital of Wuhan University from September 1 st , 2019 to July 1 st , 2021 were retrospective analyzed. Esotropia, eye alignment, stereopsis, and complications were examined at baseline (except complications), 1wk, 1, 3, and 6mo after injection., Results: The average angle of deviation before injection was (+20.24±6.80) Δ at near and (+24.76±6.43) Δ at distance, while (+5.15±5.85) Δ at near and (+7.30±6.17) Δ at distance 6mo after treatment ( P <0.05). Six months after injection, the stereopsis of patients had improved. The number of patients having no stereopsis (>800 seconds of arc) decreased from 11 to 3. The number of patients having peripheral stereopsis (300-800 seconds of arc), macular stereopsis (70-200 seconds of arc) and central concave stereopsis (≤60 seconds of arc) increased from 10 to 11, 10 to 12, and 2 to 7, respectively. At the follow-ups at 1wk, 1, 3, and 6mo after injection, success rates were 96.97%, 96.97%, 93.94% and 87.88%, respectively. One week after injection, two patients (6.07%) showed subconjunctival hemorrhage; three patients (9.09%) showed limited eye movement and one patient (3.03%) showed mild vertical strabismus. All the symptoms disappeared by the final follow-up., Conclusion: Micro-injection of BTXA can reduce diplopia and improve binocular vision function of AACE patients. Furthermore, the operation is relatively safe with few complications, making it an ideal treatment modality for AACE., (International Journal of Ophthalmology Press.)

Background: In brain, microvascular endothelial cells are exposed to various forces, including shear stress (SS). However, little is known about the effects of high shear stress (HSS) on human brain microvascular endothelial cells (HBMECs) and the underlying mechanism. The cholesterol efflux regulator ATP-binding cassette subfamily A member 1 (ABCA1) has been demonstrated to exert protective effect on HBMECs. However, whether ABCA1 is involved in the mechanism underneath the effect of HSS on HBMECs remains obscure. In the present study, a series of experiments were performed to better understand the effect of HSS on cellular processes of HBMECs and the possible involvement of ABCA1 and PI3K/Akt/eNOS in the underlying mechanisms., Results: HBMECs were subjected to physiological SS (PSS) or high SS (HSS). Cell migration was evaluated using Transwell assay. Apoptotic HBMECs were detected by flow cytometry or caspase3/7 activity. IL-1β, IL-6, MCP-1 and TNF-α levels were measured by ELISA. RT-qPCR and western blotting were used for mRNA and protein expression detection, respectively. ROS and NO levels were detected using specific detection kits. Compared to PSS, HBMECs exhibited decreased cell viability and migration and increased cell apoptosis, increased levels of inflammatory cytokines, and improved ROS and NO productions after HSS treatment. Moreover, HSS downregulated ABCA1 but upregulated the cholesterol efflux-related proteins MMP9, AQP4, and CYP46 and activated PI3K/Akt/eNOS pathway. Overexpression of ABCA1 in HBMECS inhibited PI3K/Akt/eNOS pathway and counteracted the deleterious effects of HSS. Contrary effects were observed by ABCA1 silencing. Inhibiting PI3K/Akt/eNOS pathway mimicked ABCA1 effects, suggesting that ABCA1 protects HBMECs from HSS via PI3K/Akt/eNOS signaling., Conclusion: These results advanced our understanding on the mechanisms of HSS on HBMECs and potentiated ABCA1/PI3K/Akt/eNOS pathway as therapeutic target for cerebrovascular diseases., (© 2022. The Author(s).)

The cerebrospinal fluid (CSF) immune responses in HIV-uninfected cryptococcal meningitis (CM) have not been well studied. In this study, we aimed to explore the phenotype of CSF immune response during the course of disease and to examine relationships between phenotypes and disease severity. We profiled the CSF immune response in 128 HIV-uninfected CM and 30 pulmonary cryptococcosis patients using a 27-plex Luminex cytokine kit. Principal component analyses (PCA) and logistic regression model were performed. Concentrations of 23 out of 27 cytokines and chemokines in baseline CSF were significantly elevated in CM patients compared with pulmonary cryptococcosis cases. In CM patients with Cryptococcus neoformans infection, IL-1ra, IL-9, and VEGF were significantly elevated in immunocompetent cases. Cytokine levels usually reached peaks within the first 2 weeks of antifungal treatment and gradually decreased over time. PCA demonstrated a co-correlated CSF cytokine and chemokine response consisting of Th1, Th2, and Th17 type cytokines. Prognostic analysis showed that higher scores for the PCs loading pro-inflammatory cytokines, IFN-γ, TNF-α, and IL-12; and anti-inflammatory cytokine, IL-4; and chemokines, Eotaxin, FGF-basis, and PDGF-bb; as well as lower scores for the PCs loading RANTES were associated with disease severity, as defined by a Glasgow Coma Scale of <15 or death. In conclusion, combined inflammatory responses in CSF involving both pro- and anti-inflammatory cytokines and chemokines are upregulated in HIV-uninfected CM, and associated with disease severity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jiang, Wang, Zhou, Cheng, Luo, Zhu, Qiu, Zhao, Wang, Harrison and Zhu.)

The present study evaluated the students' psychological well-being, experiences, performance, and perception of learning regional anatomy remotely. A regional anatomy remote learning curriculum was designed and learning materials were delivered virtually to 120 undergraduate medical students at Jinan University, China. All the students consented and voluntarily participated in this study by completing self-administered online questionnaires including the Zung's Self-Rating Anxiety and Depression Scales at the beginning and end of the learning session. A subset participated in focus group discussions. Most of the students (90.0%) positively evaluated the current distance learning model. More than 80% were satisfied with the content arrangement and coverage. Many students preferred virtual lectures (68.2%) and videos showing dissections (70.6%) during the distance learning sessions. However, writing laboratory reports and case-based learning were the least preferred modes of learning as they were only preferred by 23.2% and 14.1% of the students, respectively. There was no significant lockdown-related anxiety or depression reported by students using depression and anxiety scales as well as feedback from focus group discussions. The surveyed students' confidence scores in distance learning were significantly higher after 5 weeks than at the beginning of the session (3.05 ± 0.83 vs. 3.70 ± 0.71, P < 0.05). Furthermore, the present results showed no significant differences between the current group's academic performance in the unit tests as well as the final overall evaluation for different parts of the course compared to that of the previous year's cohort. The findings above were congruent with focus group discussion data that the use of the online teaching platform for regional anatomy significantly improved the students' confidence in virtual and self-directed learning and did not negatively affect their academic performance., (© 2022 American Association for Anatomy.)

Cryptococcosis is a potentially lethal disease that is primarily caused by the fungus Cryptococcus neoformans, treatment options for cryptococcosis are limited. Here, we show glucuronoxylomannan, the major polysaccharide component of C. neoformans, induces the recruitment of neutrophilic myeloid-derived suppressor cells in mice and patients with cryptococcosis. Depletion of neutrophilic myeloid-derived suppressor cells enhances host defense against C. neoformans infection. We identify C-type lectin receptor-2d recognizes glucuronoxylomannan to potentiate the immunosuppressive activity of neutrophilic myeloid-derived suppressor cells by initiating p38-mediated production of the enzyme arginase-1, which inhibits T-cell mediated antifungal responses. Notably, pharmacological inhibition of arginase-1 expression by a specific inhibitor of p38, SB202190, or an orally available receptor tyrosine kinase inhibitor, vandetanib, significantly enhances T-cell mediated antifungal responses against cryptococcosis. These data reveal a crucial suppressive role of neutrophilic myeloid-derived suppressor cells during cryptococcosis and highlight a promising immunotherapeutic application by inhibiting arginase-1 production to combat infectious diseases., (© 2022. The Author(s).)

Medical students' motivation and study strategies are crucial in determining academic performance. This study aimed to assess the motivation and learning strategies of medical students as well as their association with performance in anatomy examinations. The Motivated Strategies for Learning Questionnaire, two focus group discussions, and students' current anatomy cumulative grade point average (cGPA) were used. Generally, the medical students strongly felt that anatomy is fundamental to the practice of medicine and surgery. This result was consistent with high task value scores of 5.99 ± 1.25. They were also driven by extrinsic goal orientation (5.59 ± 1.42) and intrinsic goal orientation (5.08 ± 1.26). Most medical students typically relied on elaboration (5.35 ± 1.25) ahead of other cognitive strategies namely rehearsal (5.30 ± 1.11), organization (5.15 ± 1.34), and lowest-rated critical thinking (4.77 ± 1.19). The students also relied on resource management strategies, effort regulation (5.15 ± 1.20) and time and study environment regulation (5.03 ± 1.03) more than the moderately scored peer learning (4.95 ± 1.50) and help-seeking (4.95 ± 1.09). In the focus group discussions, students reported that they often narrate or explain to each other what they would have read and understood from anatomy lectures, tutorials, and textbooks. They also bemoaned the lack of institutional support for stress burdens. The motivation and learning strategies subscales were not correlated with anatomy cGPA. Males were driven by extrinsic goals and experienced significantly higher levels of test anxiety than females (P < 0.05). Knowing the motivation and learning strategies students employ early in the medical curriculum can be leveraged to promote self-directed learning and academic achievement., (© 2021 American Association for Anatomy.)

Adult mammals have limited potential for cardiac regeneration after injury. In contrast, neonatal mouse heart, up to 7 days post birth, can completely regenerate after injury. Therefore, identifying the key factors promoting the proliferation of endogenous cardiomyocytes (CMs) is a critical step in the development of cardiac regeneration therapies. In our previous study, we predicted that mitogen-activated protein kinase (MAPK) interacting serine/threonine-protein kinase 2 (MNK2) has the potential of promoting regeneration by using phosphoproteomics and iGPS algorithm. Here, we aimed to clarify the role of MNK2 in cardiac regeneration and explore the underlying mechanism. In vitro, MNK2 overexpression promoted, and MNK2 knockdown suppressed cardiomyocyte proliferation. In vivo, inhibition of MNK2 in CMs impaired myocardial regeneration in neonatal mice. In adult myocardial infarcted mice, MNK2 overexpression in CMs in the infarct border zone activated cardiomyocyte proliferation and improved cardiac repair. In CMs, MNK2 binded to eIF4E and regulated its phosphorylation level. Knockdown of eukaryotic translation initiation factor (eIF4E) impaired the proliferation-promoting effect of MNK2 in CMs. MNK2-eIF4E axis stimulated CMs proliferation by activating cyclin D1. Our study demonstrated that MNK2 kinase played a critical role in cardiac regeneration. Over-expression of MNK2 promoted cardiomyocyte proliferation in vitro and in vivo, at least partly, by activating the eIF4E-cyclin D1 axis. This investigation identified a novel target for heart regenerative therapy., (Copyright © 2022. Published by Elsevier Ltd.)

The purpose of this study was to investigate the effect of Geniposide on hepatic fibrosis and activation of hepatic stellate cells (HSCs) and to explore possible underlying mechanism. Human HSCs (LX-2) were treated with 5 ng/mL transforming growth factor-β1 (TGF-β1), followed by co-culture with Geniposide at various concentrations (0, 1, 2.5, 5, 10, 20, 40, 60, 80, 100 μmol/L). Cell viability was determined by MTT assay. Then, LX-2 cells were divided into control, TGF-β1 (5 ng/mL) and TGF-β1 + Geniposide (20 μmol/L) groups, and the gene and protein expression of collagen I, fibronectin, α-smooth muscle actin (α-SMA), p-Smad2 and p-Smad3 was detected by qPCR and Western blot, respectively. BALB/c mice were treated with CCl 4 (25%, 1 mL/kg) to generate a model of hepatic fibrosis (CCl 4 group), and the control group and CCl 4 + Geniposide group were administered with olive oil and CCl 4 + 40 mg/kg Geniposide, respectively. After 4 weeks of treatment, the liver function and serum hepatic fibrosis indexes of mice were detected, histological observation was performed by HE and Masson staining, and α-SMA expression in the tissue was analyzed by immunohistochemistry. Western blot was utilized for the determination of the protein expression of α-SMA, TGF-β1, p-Smad2 and p-Smad3. The results showed that Geniposide inhibited LX-2 cell proliferation. In addition, Geniposide significantly downregulated the gene and protein expression of collagen I, fibronectin and α-SMA and the expression of TGF-β1/Smad signaling-related proteins induced by TGF-β1 in vitro. Histological observations showed that Geniposide significantly inhibited CCl 4 -induced hepatic fibrosis, HSC activation and expression of TGF-β1/Smad signaling-related proteins in mice. In summary, Geniposide prevents the hepatic fibrosis and HSC activation possibly through the inhibition of the TGF-β1/Smad signaling pathway.

The trichomes of Arabidopsis thaliana serve as accumulation sites for heavy metals such as Cd 2+ , and thereby both help plants cope with heavy metal stress and detoxify the soil. These trichomes are also believed to prime plant defenses against insect herbivores in response to mechanical stimulation. Because Cd 2+ in such trichomes may be beneficial for plant defenses, we hypothesized that mechanical stimulation would enhance sequestration of Cd 2+ in trichomes. We quantified the distribution and concentration of Cd 2+ in leaves of A. thaliana, of the glabrous mutant gl1-1 of A. thaliana, and Brassica rapa L. subsp. pekinensis (Lour.) Hanelt (Chinese cabbage) and examined how these changed following mechanical stimulation of the trichomes or leaves. Light brushing or exposure to caterpillars of Spodoptera exigua led trichomes of both A. thaliana and Chinese cabbage to accumulate Cd 2+ complexes more rapidly and to a higher concentration than trichomes in unstimulated controls. Comparison to responses in leaves of gl1-1 mutants suggested that this acceleration and enhancement of Cd 2+ storage requires signaling through trichomes. In wild type A. thaliana, Cd 2+ was found exclusively in trichomes, whereas in gl1-1 mutants, Cd 2+ was found mainly in the - mesophyll cells. Results suggest a mechanobiological pathway for improving heavy metal detoxification of soils through the action of hyperaccumulator plant leaves containing non-glandular trichomes., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Elevated lipoprotein(a) [Lp(a)] is a risk factor for coronary heart disease (CHD), but there are few studies on the prediction of future cardiovascular events by Lp(a) and its LPA single nucleotide polymorphisms (SNPs). The aim of this study was to investigate whether elevated Lp(a) and its SNPs can predict cardiovascular events. We evaluated whether Lp(a) and LPA SNPs rs6415084 and rs12194138 were associated with the incidence rate and severity of CHD. All participants were followed up for 5 years. Elevated Lp(a) is an independent risk factor for the risk and severity of CHD (CHD group vs. control group: OR = 1.793, 95% CI: 1.053-2.882, p = 0.043; multiple-vessel disease group vs. single-vessel disease group: OR = 1.941, 95% CI: 1.113-3.242, p = 0.027; high GS group vs. low GS group: OR = 2.641, 95% CI: 1.102-7.436, p = 0.040). Both LPA SNPs were risk factors for CHD, and were positively associated with the severity of CHD (LPA SNPs rs6415084: CHD group vs. control group: OR = 1.577, 95% CI: 1.105-1.989, p = 0.004; multiple-vessel disease group vs. single-vessel disease group: OR = 1.613, 95% CI: 1.076-2.641, p = 0.030; high GS group vs. low GS group: OR = 1.580, 95% CI: 1.088-2.429, p = 0.024; LPA SNPs rs12194138: CHD group vs. control group: OR = 1.475, 95% CI: 1.040-3.002, p = 0.035; multiple-vessel disease group vs. single-vessel disease group: OR = 2.274, 95% CI: 1.060-5.148, p = 0.038; high GS group vs. low GS group: OR = 2.067, 95% CI: 1.101-4.647, p = 0.021). After 5 years of follow-up, elevated Lp(a) and LPA SNPs rs6415084 and rs12194138 can independently predict cardiovascular events. The increase of serum Lp(a) and LPA SNPs rs6415084 and rs12194138 are associated with increased prevalence and severity of CHD, and can independently predict cardiovascular events., (© 2022. The Author(s).)

In order to comprehensively explore multitarget mechanism and key active compounds of Artemisia argyi essential oil (AAEO) in the treatment of pressure injuries (PIs), we analyzed the biological functions and pathways involved in the intersection targets of AAEO and PIs based on network pharmacology, and the affinity of AAEO active compounds and core targets was verified by molecular docking finally. In our study, we first screened 54 effective components according to the relative content and biological activity. In total, 103 targets related to active compounds of AAEO and 2760 targets associated with PIs were obtained, respectively, and 50 key targets were overlapped by Venny 2.1.0. The construction of key targets-compounds network was achieved by the STRING database and Cytoscape 3.7.2 software. GO analysis from Matespace shows that GO results are mainly enriched in biological processes, including adrenergic receptor activity, neurotransmitter clearance, and neurotransmitter metabolic process. KEGG analysis by the David and Kobas website shows that the key targets can achieve the treatment on PIs through a pathway in cancer, PI3K-Akt signaling pathway, human immunodeficiency virus 1 infection, MAPK signaling pathway, Wnt signaling pathway, etc. In addition, molecular docking results from the CB-Dock server indicated that active compounds of AAEO had good activity docking with the first 10 key targets. In conclusion, the potential targets and regulatory molecular mechanisms of AAEO in the treatment of PIs were analyzed by network pharmacology and molecular docking. AAEO can cure PIs through the synergistic effect of multicomponent, multitarget, and multipathway, providing a theoretical basis and new direction for further study., Competing Interests: All authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Shu-ting Lu et al.)

Anatomy is a challenging preclinical subject owing to the vast amount of information that students need to master. The adoption of relevant study approaches is key to the development of a long-lasting understanding of anatomical subject matter. Phenomenographic educational research describes the medical students as using a variable mix of deep, strategic, and surface approaches to study. Continually assessing students' learning preferences and approaches is crucial for achieving the desired learning outcomes. The approaches to studying anatomy in two groups of first-year Zimbabwean medical students from two newly established medical schools were collected using the Approaches and Study Skills Inventory for Students (ASSIST) instrument and than analyzed. At least 90% of the students believed that anatomy involved reproducing knowledge or personal understanding and development. Overall, the majority of the students adopted deep and strategic approaches, while a distant minority used the surface approach. There was no significant correlation between either the students' sex or age and their preference for a specific approach to studying. The mean anatomy grades for students using a strategic approach were significantly higher than those using deep or surface approaches. The number of strategic learners was double that of deep learners among the high achievers subgroup. The strategic approach positively correlated with performance in examinations. Generally, the students shared a common understanding of the concept of anatomy learning. Studies such as this can assist with the identification of students at risk of failure and empower lecturers to recommend the adoption of more beneficial strategic and deep learner traits., (© 2021 American Association for Anatomy.)

Met tyrosine kinase, a receptor for a hepatocyte growth factor (HGF), plays a critical role in tumor growth, metastasis, and drug resistance. Mitochondria are highly dynamic and undergo fission and fusion to maintain a functional mitochondrial network. Dysregulated mitochondrial dynamics are responsible for the progression and metastasis of many cancers. Here, using structured illumination microscopy (SIM) and high spatial and temporal resolution live cell imaging, we identified mitochondrial trafficking of receptor tyrosine kinase Met. The contacts between activated Met kinase and mitochondria formed dramatically, and an intact HGF/Met axis was necessary for dysregulated mitochondrial fission and cancer cell movements. Mechanically, we found that Met directly phosphorylated outer mitochondrial membrane protein Fis1 at Tyr38 (Fis1 pY38). Fis1 pY38 promoted mitochondrial fission by recruiting the mitochondrial fission GTPase dynamin-related protein-1 (Drp1) to mitochondria. Fragmented mitochondria fueled actin filament remodeling and lamellipodia or invadopodia formation to facilitate cell metastasis in hepatocellular carcinoma (HCC) cells both in vitro and in vivo. These findings reveal a novel and noncanonical pathway of Met receptor tyrosine kinase in the regulation of mitochondrial activities, which may provide a therapeutic target for metastatic HCC., (© 2021. The Author(s).)

To observe the effect of fat-derived pellets (FDP) on wound healing in rats, the inguinal fat of rats was obtained, and the FDP were obtained after centrifugation. The cell activity and growth factor secretion of FDP were measured. The wounds in rats were created, and FDP was used to treat the wounds of rats. The phenotype of macrophages and the expression of angiogenic factors expression in wounds were measured. The cell viability in FDP remains in high level after centrifugation and the expression of vascular endothelial growth factor (VEGF) and Basic Fibroblast Growth Factor (bFGF) from FDP was observed in vitro. The FDP significantly promoted the wound healing of rats compared with that in control groups. Moreover, the expression of M2 macrophages and VEGF in FDP group were significantly higher than that in the control group. FDP is a kind of stem cell product, which can be obtained from adipose tissue by physical centrifugation. The cytotherapeutic effect of FDP makes it a promising product for wound healing in clinics.

Background: Cryptococcal meningitis (CM)-associated immune reconstitution inflammatory syndrome (IRIS) is associated with high mortality, the epidemiology and pathophysiology of which is poorly understood, especially in non-HIV populations., Objectives: We aim to explore the incidence, clinical risk factors, immunological profiles and potential influence of leukotriene A4 hydroxylase (LTA4H) on non-HIV CM IRIS populations., Methods: In this observational cohort study, 101 previously untreated non-HIV CM patients were included. We obtained data for clinical variables, 27 cerebrospinal fluid (CSF) cytokines levels and LTA4H genotype frequencies. Changes of CSF cytokines levels before and at IRIS occurrence were compared., Results: Immune reconstitution inflammatory syndrome was identified in 11 immunocompetent males, generating an incidence of 10.9% in non-HIV CM patients. Patients with higher CrAg titres (> 1:160) were more likely to develop IRIS, and titre of 1:1280 is the optimum level to predict IRIS occurrence. Baseline CSF cytokines were significantly higher in IRIS group, which indicated a severe host immune inflammation response. Four LTA4H SNPs (rs17525488, rs6538697, rs17525495 and rs1978331) exhibited significant genetic susceptibility to IRIS in overall non-HIV CM, while five cytokines were found to be associated with rs1978331, and baseline monocyte chemotactic protein 1 (MCP-1) became the only cytokine correlated with both IRIS and LTA4H SNPs., Conclusions: Our study suggested that non-HIV CM patients with high fungal burden and severe immune inflammation response were more likely to developed IRIS. LTA4H polymorphisms may affect the pathogenesis of IRIS by regulating the level of baseline CSF MCP-1., (© 2021 The Authors. Mycoses published by Wiley-VCH GmbH.)