Selenium-GPX4 axis protects follicular helper T cells from ferroptosis.

Follicular helper T (TFH) cells are a specialized subset of CD4+ T cells that essentially support germinal center responses where high-affinity and long-lived humoral immunity is generated. The regulation of TFH cell survival remains unclear. Here we report that TFH cells show intensified lipid peroxidation and altered mitochondrial morphology, resembling the features of ferroptosis, a form of programmed cell death that is driven by iron-dependent accumulation of lipid peroxidation. Glutathione peroxidase 4 (GPX4) is the major lipid peroxidation scavenger and is necessary for TFH cell survival. The deletion of GPX4 in T cells selectively abrogated TFH cells and germinal center responses in immunized mice. Selenium supplementation enhanced GPX4 expression in T cells, increased TFH cell numbers and promoted antibody responses in immunized mice and young adults after influenza vaccination. Our findings reveal the central role of the selenium-GPX4-ferroptosis axis in regulating TFH homeostasis, which can be targeted to enhance TFH cell function in infection and following vaccination.

The full activation mechanism of the adenosine A1 receptor revealed by GaMD and Su-GaMD simulations.

The full activation process of G protein-coupled receptor (GPCR) plays an important role in cellular signal transduction. However, it remains challenging to simulate the whole process in which the GPCR is recognized and activated by a ligand and then couples to the G protein on a reasonable simulation timescale. Here, we developed a molecular dynamics (MD) approach named supervised (Su) Gaussian accelerated MD (GaMD) by incorporating a tabu-like supervision algorithm into a standard GaMD simulation. By using this Su-GaMD method, from the active and inactive structure of adenosine A1 receptor (A1R), we successfully revealed the full activation mechanism of A1R, including adenosine (Ado)-A1R recognition, preactivation of A1R, and A1R-G protein recognition, in hundreds of nanoseconds of simulations. The binding of Ado to the extracellular side of A1R initiates conformational changes and the preactivation of A1R. In turn, the binding of Gi2 to the intracellular side of A1R causes a decrease in the volume of the extracellular orthosteric site and stabilizes the binding of Ado to A1R. Su-GaMD could be a useful tool to reconstruct or even predict ligand-protein and protein-protein recognition pathways on a short timescale. The intermediate states revealed in this study could provide more detailed complementary structural characterizations to facilitate the drug design of A1R in the future.

Thirteen complete chloroplast genomes of the costaceae family: insights into genome structure, selective pressure and phylogenetic relationships.

BACKGROUND: Costaceae, commonly known as the spiral ginger family, consists of approximately 120 species distributed in the tropical regions of South America, Africa, and Southeast Asia, of which some species have important ornamental, medicinal and ecological values. Previous studies on the phylogenetic and taxonomic of Costaceae by using nuclear internal transcribed spacer (ITS) and chloroplast genome fragments data had low resolutions. Additionally, the structures, variations and molecular evolution of complete chloroplast genomes in Costaceae still remain unclear. Herein, a total of 13 complete chloroplast genomes of Costaceae including 8 newly sequenced and 5 from the NCBI GenBank database, representing all three distribution regions of this family, were comprehensively analyzed for comparative genomics and phylogenetic relationships. RESULT: The 13 complete chloroplast genomes of Costaceae possessed typical quadripartite structures with lengths from 166,360 to 168,966 bp, comprising a large single copy (LSC, 90,802 - 92,189 bp), a small single copy (SSC, 18,363 - 20,124 bp) and a pair of inverted repeats (IRs, 27,982 - 29,203 bp). These genomes coded 111 - 113 different genes, including 79 protein-coding genes, 4 rRNA genes and 28 - 30 tRNAs genes. The gene orders, gene contents, amino acid frequencies and codon usage within Costaceae were highly conservative, but several variations in intron loss, long repeats, simple sequence repeats (SSRs) and gene expansion on the IR/SC boundaries were also found among these 13 genomes. Comparative genomics within Costaceae identified five highly divergent regions including ndhF, ycf1-D2, ccsA-ndhD, rps15-ycf1-D2 and rpl16-exon2-rpl16-exon1. Five combined DNA regions (ycf1-D2 + ndhF, ccsA-ndhD + rps15-ycf1-D2, rps15-ycf1-D2 + rpl16-exon2-rpl16-exon1, ccsA-ndhD + rpl16-exon2-rpl16-exon1, and ccsA-ndhD + rps15-ycf1-D2 + rpl16-exon2-rpl16-exon1) could be used as potential markers for future phylogenetic analyses and species identification in Costaceae. Positive selection was found in eight protein-coding genes, including cemA, clpP, ndhA, ndhF, petB, psbD, rps12 and ycf1. Maximum likelihood and Bayesian phylogenetic trees using chloroplast genome sequences consistently revealed identical tree topologies with high supports between species of Costaceae. Three clades were divided within Costaceae, including the Asian clade, Costus clade and South American clade. Tapeinochilos was a sister of Hellenia, and Parahellenia was a sister to the cluster of Tapeinochilos + Hellenia with strong support in the Asian clade. The results of molecular dating showed that the crown age of Costaceae was about 30.5 Mya (95% HPD: 14.9 - 49.3 Mya), and then started to diverge into the Costus clade and Asian clade around 23.8 Mya (95% HPD: 10.1 - 41.5 Mya). The Asian clade diverged into Hellenia and Parahellenia at approximately 10.7 Mya (95% HPD: 3.5 - 25.1 Mya). CONCLUSION: The complete chloroplast genomes can resolve the phylogenetic relationships of Costaceae and provide new insights into genome structures, variations and evolution. The identified DNA divergent regions would be useful for species identification and phylogenetic inference in Costaceae.

Oxidation Analysis of l-Cysteine with a Chiral Sensor Based on Quantum Weak Measurement.

l-Cysteine, distinguished by its possession of reactive sulfhydryl groups within its molecular structure, plays a significant role in both biological systems and the pharmaceutical industry. It stands not only as a natural component integral to the constitution of glutathione but also as the principal precursor for the synthesis of l-cystine through an oxidation reaction. This study endeavors to introduce a novel approach to l-cysteine analysis, capitalizing on its optical activity, whereby an optical rotation detection system grounded in the principles of quantum weak measurement is proffered. The optical rotation angle corresponding to the concentration of chiral solutions can be accurately ascertained through spectral analysis. In practical implementation, a chiral sensing system, boasting a sensitivity of 372 nm/rad, was meticulously constructed, leveraging the concept of weak value amplification. Then, the real-time monitoring of chemical reactions involving l-cysteine and dimethyl sulfoxide was performed. Under the specific experimental conditions outlined in this investigation, it was observed that the oxidation process culminated within approximately 12 h. The application of weak measurement-based chiral sensors holds immense potential, providing robust technical support for real-time monitoring in fields such as chiral analysis and the synthesis of chiral pharmaceutical compounds.

Soluble humic acid suppresses plant immunity and ethylene to promote soybean nodulation.

Symbiotic nitrogen fixation (SNF) is a crucial process for nitrogen geochemical cycling and plant-microbe interactions. Water-soluble humic acid (WSHM), an active component of soil humus, has been shown to promote SNF in the legume-rhizobial symbiosis, but its molecular mechanism remains largely unknown. To reveal the SNF-promoting mechanism, we conducted transcriptomic analysis on soybean treated with WSHM. Our findings revealed that up- and downregulated differentially expressed genes (DEGs) were mainly involved in plant cell-wall/membrane formation and plant defence/immunity in the early stage, while the late stage was marked by the flavonoid synthesis and ethylene biosynthetic process. Further study on representative DEGs showed that WSHM could inhibit GmBAK1d-mediated immunity and BR signalling, thereby promoting rhizobial colonisation, infection, and nodulation, while not favoring pathogenic bacteria colonisation on the host plant. Additionally, we also found that the ethylene pathway is necessary for promoting the soybean nodulation by WSHM. This study not only provides a significant advance in our understanding of the molecular mechanism of WSHM in promoting SNF, but also provides evidence of the beneficial interactions among the biostimulator, host plant, and soil microbes, which have not been previously reported.

Clinical analysis of 314 patients with high-grade squamous intraepithelial lesion who underwent total hysterectomy directly: a multi-center, retrospective cohort study.

OBJECTIVE: To identify the risk factors of cervical high-grade squamous intraepithelial lesion(HSIL) complicated with occult cervical cancer and standardize the management of initial treatment for HSIL. METHOD: The clinical data of patients who underwent total hysterectomy directly due to HSIL in the obstetrics and gynecology department of two tertiary hospitals and three secondary hospitals from 2018 to 2023 were collected. Their general characteristics, pathological parameters and survival status were analyzed. Logistic regression model was used to analyze the correlation between clinical parameters and postoperative pathological upgrading. RESULT: 1. Among the 314 patients with HSIL who underwent total hysterectomy directly, 73.2% were from primary hospitals. 2. 25 patients (7.9%) were pathologically upgraded to cervical cancer, all of which were early invasive cancer. 3. Up to now, there was no recurrence or death in the 25 patients with early-stage invasive cancer, and the median follow-up period was 21 months(range 2-59 months). 4. Glandular involvement(OR 3.968; 95%CI 1.244-12.662) and lesion range ≥ 3 quadrants (OR 6.527; 95% CI 1.78-23.931), HPV 16/18 infection (OR 5.382; 95%CI 1.947-14.872), TCT ≥ ASC-H (OR 4.719; 95%CI 1.892-11.766) were independent risk factors that affected the upgrading of postoperative pathology. 5. The area under the curve (AUC) calculated by the Logistic regression model was 0.840, indicating that the predictive value was good. CONCLUSION: There is a risk of occult cervical cancer in patients with HSIL. Glandular involvement, Lesion range ≥ 3 quadrants, HPV 16/18 infection and TCT ≥ ASC-H are independent risk factors for HSIL combined with occult cervical cancer. The prognosis of biopsy-proved HSIL patients who underwent extrafascial hysterectomy and unexpected early invasive cancer was later identified on specimen may be good.

Mitochondria complex I deficiency in Candida albicans arrests the cell cycle at S phase through suppressive TOR and PKA pathways.

How mutations in mitochondrial electron transport chain (ETC) proteins impact the cell cycle of Candida albicans was investigated in this study. Using genetic null mutants targeting ETC complexes I (CI), III (CIII), and IV (CIV), the cell cycle stages (G0/G1, S phase, and G2/M) were analyzed via fluorescence-activated cell sorting (FACS). Four CI null mutants exhibited distinct alterations, including extended S phase, shortened G2/M population, and a reduction in cells size exceeding 10 µM. Conversely, CIII mutants showed an increased population in G1/G0 phase. Among four CI mutants, ndh51Δ/Δ and goa1Δ/Δ displayed aberrant cell cycle patterns correlated with previously reported cAMP/PKA downregulation. Specifically, nuo1Δ/Δ and nuo2Δ/Δ mutants exhibited increased transcription of RIM15, a central hub linking cell cycle with nutrient-dependent TOR1 and cAMP/PKA pathways and Snf1 aging pathway. These findings suggest that suppression of TOR1 and cAMP/PKA pathways or enhanced Snf1 disrupts cell cycle progression, influencing cell longevity and growth among CI mutants. Overall, our study highlights the intricate interplay between mitochondrial ETC, cell cycle, and signaling pathways.

An evolutionarily diverged mitochondrial protein controls biofilm growth and virulence in Candida albicans.

A forward genetic screening approach identified orf19.2500 as a gene controlling Candida albicans biofilm dispersal and biofilm detachment. Three-dimensional (3D) protein modeling and bioinformatics revealed that orf19.2500 is a conserved mitochondrial protein, structurally similar to, but functionally diverged from, the squalene/phytoene synthases family. The C. albicans orf19.2500 is distinguished by 3 evolutionarily acquired stretches of amino acid inserts, absent from all other eukaryotes except a small number of ascomycete fungi. Biochemical assays showed that orf19.2500 is required for the assembly and activity of the NADH ubiquinone oxidoreductase Complex I (CI) of the respiratory electron transport chain (ETC) and was thereby named NDU1. NDU1 is essential for respiration and growth on alternative carbon sources, important for immune evasion, required for virulence in a mouse model of hematogenously disseminated candidiasis, and for potentiating resistance to antifungal drugs. Our study is the first report on a protein that sets the Candida-like fungi phylogenetically apart from all other eukaryotes, based solely on evolutionary "gain" of new amino acid inserts that are also the functional hub of the protein.

Severity Identification of Graves Orbitopathy via Random Forest Algorithm.

This study aims to establish a random forest model for detecting the severity of Graves Orbitopathy (GO) and identify significant classification factors. This is a hospital-based study of 199 patients with GO that were collected between December 2019 and February 2022. Clinical information was collected from medical records. The severity of GO can be categorized as mild, moderate-to-severe, and sight-threatening GO based on guidelines of the European Group on Graves' orbitopathy. A random forest model was constructed according to the risk factors of GO and the main ocular symptoms of patients to differentiate mild GO from severe GO and finally was compared with logistic regression analysis, Support Vector Machine (SVM), and Naive Bayes. A random forest model with 15 variables was constructed. Blurred vision, disease course, thyroid-stimulating hormone receptor antibodies, and age ranked high both in mini-decreased gini and mini decrease accuracy. The accuracy, positive predictive value, negative predictive value, and the F1 Score of the random forest model are 0.83, 0.82, 0.86, and 0.82, respectively. Compared to the three other models, our random forest model showed a more reliable performance based on AUC (0.85 vs. 0.83 vs. 0.80 vs. 0.76) and accuracy (0.83 vs. 0.78 vs. 0.77 vs. 0.70). In conclusion, this study shows the potential for applying a random forest model as a complementary tool to differentiate GO severity.

Neutrophil extracellular traps (NETs) and Th-2 dominant immune responses in chronic granulomatous chromobalstomycosis.

Chromoblastomycosis (CBM), a chronic, granulomatous, suppurative mycosis of the skin and subcutaneous tissue, is caused by several dematiaceous fungi. The formation of granulomas, tissue proliferation, and fibrosis in response to these pathogenic fungi is believed to be intricately linked to host immunity. To understand this complex interaction, we conducted a comprehensive analysis of immune cell infiltrates, neutrophil extracellular traps (NETs) formation, and the fibrosis mechanism in 20 CBM lesion biopsies using immunohistochemical and immunofluorescence staining methods. The results revealed a significant infiltration of mixed inflammatory cells in CBM granulomas, prominently featuring a substantial presence of Th2 cells and M2 macrophages. These cells appeared to contribute to the production of collagen I and III in the late fibrosis mechanism, as well as NETs formation. The abundance of Th2 cytokines may act as a factor promoting the bias of macrophage differentiation toward M2, which hinders efficient fungal clearance while accelerates the proliferation of fibrous tissue. Furthermore, the expression of IL-17 was noted to recruit neutrophils, facilitating subsequent NETs formation within CBM granulomas to impede the spread of sclerotic cells. Understanding of these immune mechanisms holds promise for identifying therapeutic targets for managing chronic granulomatous CBM.

Characterizing Anti-Vaping Posts for Effective Communication on Instagram Using Multimodal Deep Learning.

INTRODUCTION: Instagram is a popular social networking platform for sharing photos with a large proportion of youth and young adult users. We aim to identify key features in anti-vaping Instagram image posts associated with high social media user engagement by artificial intelligence. AIMS AND METHODS: We collected 8972 anti-vaping Instagram image posts and hand-coded 2200 Instagram images to identify nine image features such as warning signs and person-shown vaping. We utilized a deep-learning model, the OpenAI: contrastive language-image pre-training with ViT-B/32 as the backbone and a 5-fold cross-validation model evaluation, to extract similar features from the Instagram image and further trained logistic regression models for multilabel classification. Latent Dirichlet Allocation model and Valence Aware Dictionary and sEntiment Reasoner were used to extract the topics and sentiment from the captions. Negative binomial regression models were applied to identify features associated with the likes and comments count of posts. RESULTS: Several features identified in anti-vaping Instagram image posts were significantly associated with high social media user engagement (likes or comments), such as educational warnings and warning signs. Instagram posts with captions about health risks associated with vaping received significantly more likes or comments than those about help quitting smoking or vaping. Compared to the model based on 2200 hand-coded Instagram image posts, more significant features have been identified from 8972 AI-labeled Instagram image posts. CONCLUSION: Features identified from anti-vaping Instagram image posts will provide a potentially effective way to communicate with the public about the health effects of e-cigarette use. IMPLICATIONS: Considering the increasing popularity of social media and the current vaping epidemic, especially among youth and young adults, it becomes necessary to understand e-cigarette-related content on social media. Although pro-vaping messages dominate social media, anti-vaping messages are limited and often have low user engagement. Using advanced deep-learning and statistical models, we identified several features in anti-vaping Instagram image posts significantly associated with high user engagement. Our findings provide a potential approach to effectively communicate with the public about the health risks of vaping to protect public health.

Topology and giant circular dichroism of enantiomorphic Kagome bands in a designed covalent organic framework.

Covalent organic frameworks (COFs) are an emerging class of crystalline organic materials that have shown potential to be a new physical platform. In this work, a designed COF named AB-COF, which has novel enantiomorphic Kagome bands, is proposed and a feasible route to synthesize it is given. Via a combination of first-principles calculations and tight-binding analysis, we investigate the electronic structures and the phase interference of the COF. It becomes topologically nontrivial when doping one iodine atom in a unit cell. The Berry curvatures of the valence band (VB) and conduction band (CB) of the iodine-doped AB-COF show opposite values and different distributions. This provides an opportunity to study the new mechanism of circular dichroism from the different Berry curvatures of the VB and CB. Surprisingly, the circular-dichroism dissymmetry factor of AB-COF reaches a theoretical maximum value, and the oscillator strength data are in agreement with this result. When two iodine atoms are doped in a unit cell, the Berry curvatures of the VB and CB also have different values, but with more symmetry and similar distributions. This behavior enhances the circular dichroism with a wider range of dissymmetric absorption, and the circular dichroism dissymmetry factor also reaches its theoretical maximum value.

Enantiomorphic kagome bands in a two-dimensional covalent organic framework with non-trivial magnetic and topological properties.

The kagome lattice is one of the most intriguing topics to study. It has a frustrated flat band touching a set of Dirac bands and can possess various promising properties, such as ferromagnetism, superconductivity, and a non-trivial topology. Covalent organic frameworks (COFs) are a rare type of inorganic material, however, they can provide a platform for generating certain required lattices. Based on first-principles density functional theory calculations, we show that a newly synthesized two-dimensional COF named COF-SH has novel enantiomorphic kagome bands, which include two sets of flat bands touching the Dirac bands around the Fermi level. The Bloch wave of the flat-valence band at the K-point shows the kagome nature of the phase interference. Under charge doping, the COF-SH exhibits a ferromagnetic ground state. Moreover, when COF-SH is doped with iodine atoms, a sizable gap in the system is opened between the flat bands and the Dirac bands due to the spin-orbit coupling (SOC) effect. Meanwhile, the spin degeneracy is lifted since the organic layer loses electrons due to the oxidizing property of iodine. In addition, our tight-binding analysis with the SOC effect shows that the flat valence band separates from the Dirac bands and holds a nonzero Chern number. Consequently, this I-doped COF can give rise to a quantum anomalous Hall effect.

Photodynamic application in diagnostic procedures and treatment of non-melanoma skin cancers.

OPINION STATEMENT: Skin tumors commonly seen in dermatology are involved in all layers of the skin and appendages. While biopsy of affected skin remains an essential method to confirm diagnosis and to predicate tumor prognosis, it has its limitations. Recently, photodynamic diagnosis (PDD) has demonstrated high sensitivity in detecting affected skin and mucosal tissues, providing valuable guidance for precision surgery to resect skin and mucosal tumors. In this review, we summarized the literatures concerning the applications of PDD in diagnostic process and treatment of skin and mucosal conditions such as actinic keratoses (AK), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Bowen's disease (BD) and extramammary Paget's disease (EMPD). The findings suggest that PDD holds substantial promise for expanding clinical applications and deserves further research exploration.

Radioactivity of inert construction and demolition waste from Hong Kong and environmental assessment for marine trial reclamation in Guanghai Bay.

Inert construction and demolition waste from Hong Kong (HK public fills) has been used for marine trial reclamation in the Guanghai Bay (GHWT) of the Chinese Mainland. However, an environmental assessment of HK public fills is necessary due to higher radioactivity in HK soils than typical global levels. Here, radiation dose rate, gamma radionuclides and gross beta of HK public fills were analyzed. The origin information was explored using natural primordial radionuclides as fingerprints. Our data show that radiation dose rate of HK public fills before disposal was 0.14-0.54 (0.33 ± 0.03) µSv/h (n = 16,722 data with 2787 ships) in 2014, which is less than the GHWT background. Monthly detection of 238U, 226Ra, 210Pb, 232Th, 228Th, 40K, and gross beta in HK public fills was conducted on three random ships. Their specific activities were <6.27-155.5, 58.7-98.7, <7.83-238.2,97.9-168.6, 87.1-136.0, 463.1-1,018, and 1047-1658 Bq/kgDW, respectively. These results suggest that the radioactivity levels of HK public fills are essentially the same as the GHWT background. The study assessed potential risks using various indices icluding Raeq (Radium equivalent activity), Hex (External radiation hazard index), Hin (Internal radiation hazard index), Iγ (Gamma index), AUI (Activity utilization index), AUI (Activity utilization index), E (Annual effective dose), AGDE (Annual gonadal dose equivalent), RLI (Representative level index), Din (Indoor air absorbed dose rate), Dout (Outdoor air absorbed dose rate), and ELCR (Excess lifetime cancer risk). The study suggests that HK public fills should be used for the trial reclamation rather than building-house materials. This provides valuable insights for the resource utilization and minimizing environmental pollution of HK public fills. The aim is to offer fundamental technical assistance for future waste resource utilization, ecological protection, and restoration in the Guangdong-Hong Kong-Macao Greater Bay Area.

Improving the Application of Prothrombin Time-Derived Fibrinogen Assay Through Value Transfer from the Von Clauss Method.

BACKGROUND: This study aimed to improve the accuracy of the fibrinogen (Fib) prothrombin time-derived (PT-der) method. To achieve this, a value transfer method was introduced for calibration, and its effectiveness was assessed. METHODS: The PT-der Fib assay was calibrated by pooled samples (assigned by the von Clauss method) in three different ways: 1) multipoint calibration using an automatic dilution system, 2) multipoint calibration using a manual dilution method, and 3) manual calibration with multiple concentrations. Three calibration equations (1, 2, and 3) were obtained and an optimal equation was selected by comparing the detection results of the von Clauss method with the PT-der method. Subsequently, the optimal equation was assessed for an accuracy limit, and linear analysis and reference interval verification were performed following the guidelines (EP15-A and EP6-A) issued by the CLSI. RESULTS: Compared with the other two equations (equation 1 and 2), equation 3, available from manual calibration with multiple concentrations, showed a better performance for the PT-der determination in a primary cohort (n = 208), and a good agreement (99% of the results between 1.52 and 6.30 g/L were interchangeable) was validated (n = 3226). The reference interval was also verified in almost all healthy individuals (39/40). However, the discrep-ancy between the two methods was observed in several specific conditions, such as hyperfibrinolysis. CONCLUSIONS: Manual calibration with multiple concentrations is better for the Fib PT-der method assay. As a rapid, accurate, and economical test, the performance of the Fib PT-der method has been verified and may be more applicable than before.

Three-dimensional soft tissue reconstruction and volume measurement used for the diagnosis of dysthyroid optic neuropathy.

PURPOSE: Dysthyroid optic neuropathy (DON) leads to vision loss. This study aimed to investigate a new method that can directly evaluate the change in muscle cone inner volume (MCIV) and distinguish DON orbits from non-DONs. MATERIALS AND METHODS: This study included 54 patients (108 orbits) who were diagnosed with thyroid eye disease and treated at the Beijing Tongren Hospital between December 2019 and September 2021. The extraocular muscle volume (EOMV), orbital fat volume (OFV), and bony orbit volume (BOV) of the patients were measured using three-dimensional reconstruction. MCIV was measured using artificially defined boundaries. The associations between these volumes and clinical indicators were studied, and the diagnostic efficacy of these volumes for DON was described using receiver operating characteristic (ROC) curves. RESULTS: The ROC curve showed that the area under the curve of MCIV/BOV (%) combined with EOMV/BOV (%) reached 0.862 (p < 0.001), with a sensitivity of 85.7% and a specificity of 76.1%. CONCLUSION: The combination of MCIV/BOV (%) and EOMV/BOV (%) is a good indicator for the diagnosis of DON, which aids in the early detection and intervention of DON.

Adult classic Bartter syndrome: a case report with 5-year follow-up and literature review.

Bartter syndrome (BS) is a rare, inherited salt-losing renal tubular disorder characterized by secondary hyperaldosteronism, hypokalemia, hypochloremia, metabolic alkalosis, and low-to-normal blood pressure. Classic BS, or BS Type 3, the most common subtype in the Asian population, is caused by a molecular defect in ClC-Kb, a voltage-gated chloride channel in renal tubules, due to CLCNKB gene mutation. Because the onset of BS is more common in children than in adults, the diagnosis, treatment outcomes, genotype/phenotype association, and follow-up of adult-onset BS Type 3 are limited. This case report describes the findings in a 20-year-old man who was admitted with hypokalemic paralysis, with clinical manifestations were similar to those of Gitelman syndrome (GS); however, the patient was later diagnosed to have BS Type 3 through genetic testing (NM_000085.4 (CLCNKB): c.1052G>T). A literature review showed that no homozygous mutations have been reported to date. After 5 years of treatment and follow-up, we found that this genotype requires high levels of potassium and is prone to urinary protein and metabolic syndrome. Distinguishing adult-onset BS from GS is challenging in clinical practice. However, genetic diagnosis can help solve this problem effectively, and genotypes play a guiding role in treatment planning.

Proteome-Wide Analysis of Lysine 2-Hydroxyisobutyrylation in Aspergillus fumigatus.

Aspergillus fumigatus is the significant causative agent in cases of invasive aspergillosis, leading to a high mortality rate in immunocompromised patients. A comprehensive understanding of its growth patterns and metabolic processes within the host is a critical prerequisite for the development of effective antifungal strategies. Lysine 2-hydroxyisobutyrylation (Khib) is a highly conserved protein posttranslational modifications (PTM) found in various organisms. In this study, we investigate the biological impact of Khib in A. fumigatus. Using a combination of antibody enrichment with the conventional LC-MS/MS method, the pattern of Khib-modification in proteins and their respective sites were analyzed in a wild type strain of A. fumigatus. Our findings revealed 3494 Khib-modified proteins with a total of 18,091 modified sites in this strain. Functional enrichment analysis indicated that these Khib-modified proteins participate in a diverse range of cellular functions, spanning various subcellular locations such as ribosome biosynthesis, protein synthesis and nucleocytoplasmic transport. Notably, when compared with other reported eukaryotes, A. fumigatus exhibited consistently higher numbers of Khib-modified proteins, suggesting the potential significance of this modification in this organism. An interesting observation is the prevalence of Khib modifications in most enzymes involved in the ergosterol synthesis pathway. The insights gathered from this study provide new avenue for studying PTM-associated mechanisms in fungal growth and offer potential implication for antifungal drug development.