Cryptococcosis is a life-threatening fungal infection with global public health impact, affecting both immunocompromised individuals and the general population. Accurate clinical management requires differentiation of Cryptococcus species and detection of subclinical infections. However, current diagnostic methods suffer from limited sensitivity and, notably, selectivity. Here, we report a highly sensitive and selective electrochemical immunosensor for rapid and simple serological diagnosis of cryptococcosis. The sensor employs novel multi-epitope chimeric proteins (A, B, C, and D) directly anchored onto a molybdenum disulfide (MoS2)-functionalized gold electrode, enabling simplified construction and stable bioreceptor immobilization without chemical cross-linkers. Comprehensive physicochemical characterization by SPR, AFM, EDS, SEM, Raman spectroscopy, and electrochemical techniques provided essential structural information governing the synergistic integration of MoS2 and chimeric proteins. Using Square Wave Voltammetry (SWV), a comparative evaluation against human serum samples identified Protein D as the main bioreceptor, providing the highest discrimination between positive and negative groups. The optimized MoS2/Protein D immunosensor achieved an outstanding limit of detection (LOD) of 0.124 fmol L-1 and a wide linear range spanning from fmol L-1 to nmol L-1. Clinical validation via ROC curve analysis demonstrated excellent diagnostic performance, with 100% sensitivity, 87.5% specificity, and an area under the curve (AUC) of 0.987. Furthermore, the sensor exhibited high selectivity against a panel of five other systemic mycoses (aspergillosis, histoplasmosis, sporotrichosis, coccidioidomycosis, and paracoccidioidomycosis), overcoming the specificity gaps of routine assays. These results represent a significant advance for clinical practice and highlight the potential of simple electrochemical approaches to resolve complex diagnostic problems.
Trichophyton rubrum is a highly prevalent dermatophyte re for superficial mycoses affecting keratinized tissues such as skin, hair and nails. Its ability to colonize these tissues is attributed to its keratolytic activity and adaptability to different environmental conditions. This retrospective study included cases of dermatophytosis caused by Trichophyton rubrum diagnosed at the Parasitology-Mycology Laboratory of the Mohammed VI University Hospital in Oujda over a period of four and a half years, from January 7, 2020, to July 7, 2024. Each sample was examined by direct microscopy after clarification with 30 % KOH and cultured on Sabouraud media at 25 °C. This study aims to investigate the epidemiological and mycological characteristics of patients diagnosed with Trichophyton rubrum dermatophytosis. Trichophyton rubrum dermatophytosis was mycologically confirmed in 287 of the 1328 samples received during the study period. The mean age of our patients was 52 years, with extremes ranging from 7 to 98 years. Our series was characterized by a M/F sex ratio of 1. Onychomycosis represented 67.8 % of all collected samples. Among the affected patients, 168 cases (58.74 %) involved onychomycosis of the feet, while 25 cases (8.74 %) involved onychomycosis of the hands. Additionally, 71 patients (24.83 %) presented with scales, and 22 patients (7.69 %) exhibited intertrigo. Among all collected samples, 68.64 % were positive on direct examination after clarification with KOH 30 %. Trichophyton rubrum is the most widespread dermatophyte worldwide. Direct examination and mycological culture are complementary techniques for accurate diagnosis. Further epidemiological studies across Morocco are needed for meaningful comparisons.
In vitro co-culture models of human cells and microbial pathogens offer a controlled system to study host-pathogen interactions. This chapter details the methods to establish such co-culture models for a fungal and an amoebic infection using two different human cell lines. Employing this experimental system allows the researcher to evaluate MIF's contribution to infection-driven host cell death and pro-inflammatory gene expression.
Our aim was to record current susceptibility results of genital yeast isolates and to compare the results to the previous report covering the period 2001-2015. Genital yeast isolates had their antifungal susceptibility determined by disc diffusion or minimum inhibitory concentration following standard methods. Sequential isolates from the same person had their initial and last susceptibility results compared. Disc testing was performed on 1,307 initial isolates; 17 (1.3%) were from males. The most frequent isolates were Candida albicans (64%), Nakaseomyces glabratus complex (17%) and Candida parapsilosis complex (7%). While 94% of isolates were susceptible to clotrimazole, susceptibility for other azoles ranged from 62% to 84%. All isolates were susceptible to nystatin. Isolates non-susceptible to one topical azole were often resistant to all azoles tested. For fluconazole, itraconazole and miconazole fewer isolates were susceptible than in the previous time period. The susceptibility to clotrimazole did not change. One hundred and eight women had sequential isolates, range 2-5, collected 1 week to 75 months apart, median 6 months. Four pairs (4%) had a change from susceptible to resistant, all for miconazole, suggesting increased resistance. All latter isolates were susceptible to at least two other azoles and nystatin. There appears to have been an increase in antifungal resistance to several topical agents used for genital yeast infections. However, in a previously susceptible isolate, treatment failure seldom indicates a change to antifungal resistance. Women with recurrent vulvovaginal yeast infection can be reasonably treated empirically while identification and susceptibility results are awaited.
Freeze-thaw (FT) stress compromises protein stability through ice crystal formation and exposure to air-liquid and ice-liquid interfaces. This study investigated whether deaeration could mitigate Human Serum Albumin (HSA) aggregation by limiting gas-mediated interfacial stress. Tween 80 and trehalose were included to evaluate deaeration efficiency in the presence of common formulation components. The study demonstrated that deaeration using either PTFE or glass stirring consistently reduced dissolved oxygen (DO) from ~ 85% to ~ 20%, and that the extent of gas removal was independent of Tween 80 or trehalose concentration. SEC-HPLC analysis confirmed > 94% HSA monomer retention, with minimal loss attributable to deaeration. Most importantly, subvisible particles exhibited by microflow imaging (MFI) revealed the protective effect of dissolved gas reduction, with deaerated samples consistently showing lower aggregation (~ 1000 to ~ 2500 particles/mL) compared to untreated HSA samples with higher aggregation (~ 2000 to ~ 6500 particles/mL) following freezing at -80ºC. Crucially, thawing the protein samples under vacuum to prevent air redissolution preserved low dissolved air content through five FT cycles, resulting in lower aggregation than samples thawed at atmospheric pressure. The combination of deaeration process and thawing under vacuum serve as a holistic engineering approach to manage dissolved air content in protein solution and reduce the overall freeze-induced stress on HSA protein formulations.
Allergic bronchopulmonary aspergillosis (ABPA) is defined as a type I hypersensitivity reaction against allergens derived from Aspergillus spp., ubiquitous fungi present in various environments. Annually, the disease contributes a significant proportion to global morbidity and mortality, relative to other fungal diseases. Although known to affect populations worldwide, the exact pathogenesis of the disease from environmental to clinically-pertinent isolates and the basis for the emergence of antifungal resistance, a known by-product of unregulated prescription and use of drugs targeted at specific factors involved in forming fungal structural elements (i.e., ergosterol, chitin) and mediating survival mechanisms (i.e., fungal metabolism, DNA/RNA synthesis), remains poorly understood. Here, we focus on the role of the one health approach in combating the environment-host transition and mitigating the emergence of antifungal resistance. This includes the synthesis of current literature relevant to the subsequent insights on strategies to control the spread of the disease. From the findings of the present review, novel approaches to manage the incidence of ABPA and reduce the overall disease burden can be developed on a global scale. Perspectives utilizing the One Health approach has emerged as a prominent future direction for health programs worldwide, geared towards reducing the incidence and overall burden of fungal respiratory infections, such as ABPA.
Objective: To investigate the bronchoscopic features of invasive pulmonary aspergillosis (IPA) and to summarize the clinical efficacy of comprehensive bronchoscopic interventional therapy. Methods: A retrospective analysis was conducted on the clinical data of 11 patients with IPA who received comprehensive bronchoscopic interventional therapy at Beijing Tsinghua Changgung Hospital between December 2018 and December 2024. The therapeutic efficacy and safety were evaluated. Results: Among the 11 patients, 7 were male and 4 were female, with an age range of 14 to 69 years (mean 45.8±17.6 years). Underlying diseases included diabetes mellitus (4 cases), hematological malignancies (2 cases), solid tumors (2 cases), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (1 case), high IgE recurrent infection syndrome (1 case) and allergic bronchopulmonary aspergillosis (1 case). Chest CT findings showed multi-lobar involvement in nine cases and single-lobar involvement in two cases. Bronchoscopy revealed obstructive white necrotic material within the airways in four cases, purulent secretions in four cases, and bronchopulmonary cavity fistula in three cases. Pathological examination of the necrotic material confirmed the presence of abundant Aspergillus hyphae. All patients received systemic antifungal therapy. Local treatments included aerosolized amphotericin B deoxycholate inhalation in nine cases and bronchoscopic local drug perfusion in all 11 cases. Bronchoscopic interventional procedures included forceps removal of lesions in four cases, with one case experiencing grade Ⅲ hemorrhage. No severe complications such as pneumothorax occurred. Following treatment, clinical cure was achieved in six cases (54.5%) and significant improvement in five cases (45.5%), with no deaths. During the one-year follow-up, no recurrence was observed in 10 cases. Conclusions: IPA commonly occurs in immunocompromised hosts, with bronchoscopic findings often revealing airway obstruction caused by whitish necrotic material and/or secretions. An integrated therapeutic strategy combining systemic and local antifungal therapy with bronchoscopic interventional treatment can significantly enhance clinical efficacy and demonstrate a favorable safety profile. 目的： 探讨侵袭性肺曲霉病（IPA）的支气管镜下特征，总结支气管镜介入综合治疗的临床效果。 方法： 回顾性分析2018年12月至2024年12月北京清华长庚医院收治的11例接受支气管镜介入综合治疗的IPA患者临床资料，评估其疗效与安全性。 结果： 11例患者中男性7例、女性4例，年龄14~69（45.8±17.6）岁。基础疾病包括糖尿病4例、白血病2例、肝癌2例、抗中性粒细胞胞浆抗体（ANCA）相关性血管炎1例、高IgE反复感染综合征1例、变应性支气管肺曲霉病1例。胸部CT显示多肺叶受累9例，单肺叶受累2例。支气管镜下主要表现为气道内白色坏死物阻塞（4例），其次为脓性分泌物（4例）和支气管肺空洞瘘（3例）；坏死物病理检查均见大量曲霉菌丝。所有患者均接受全身抗真菌治疗，局部药物治疗包括两性霉素B脱氧胆酸盐雾化吸入治疗9例，支气管镜下局部灌注治疗11例。支气管镜介入治疗包括钳除病灶（4例），其中1例发生Ⅲ级出血，无气胸等严重并发症。治疗后临床治愈6例（54.5%），疗效显著5例（45.5%），无死亡病例；随访1年，10例未见复发。 结论： IPA好发于免疫抑制宿主，支气管镜下常见白色坏死物和（或）脓性分泌物堵塞气道；全身、局部药物治疗联合支气管镜介入治疗的综合策略，可显著提高临床疗效，安全性良好。.
Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease triggered by sensitization to Aspergillus fumigatus or other Aspergillus species, with 1.0%-3.5% incidence in asthma patients and 7%-15% incidence in cystic fibrosis patients. It is more common in patients with asthma or cystic fibrosis. Clinical manifestations include recurrent bronchial obstruction, cough, pulmonary infiltrates, and bronchiectasis. However, its actual incidence is likely underestimated due to complex diagnostic criteria and insufficient clinical awareness. To standardize the integrated traditional Chinese and western medicine practice for ABPA, exert the advantage of synergistic efficacy of Chinese and western medicine, and improve the comprehensive diagnostic and therapeutic level, the Professional Committee of Allergy of the Chinese Association of Integrated Traditional and western Medicine organized multidisciplinary experts to formulate this consensus. This consensus defines diagnostic criteria, clinical classification and long-term management plans of ABPA, emphasizes the importance of environmental control and screening in high-risk populations, and systematically outlines an integrated diagnosis and treatment strategy combining western and traditional Chinese medicine. Western medicine is based on corticosteroids and antifungal agents, with biologics such as omalizumab representing an emerging option, while traditional Chinese medicine contributes through syndrome differentiation and treatment-addressing patterns such as "wind invading the lung" and "phlegm-stasis binding"-combined with proprietary Chinese medicines and acupuncture to enhance efficacy, with the aim of providing standardized guidance for clinical practice. 变应性支气管肺曲霉病（ABPA）是一种由烟曲霉或其他曲霉属真菌致敏引发的变态反应性肺部疾病，其患病率在哮喘患者中为1.0%~3.5%，囊性纤维化患者中达7%~15%，多见于哮喘或囊性纤维化患者，临床表现为反复支气管阻塞、咳嗽、肺部浸润及支气管扩张，但因诊断标准复杂且临床认识不足，实际发病率可能被低估。为了规范ABPA的中西医结合诊疗实践，发挥中西医协同增效的优势，提升综合诊疗水平，中国中西医结合学会变态反应专业委员会组织多学科专家撰写本共识。本共识明确了ABPA的诊断标准、临床分类及长期管理方案，强调环境控制与高风险人群筛查的重要性，并系统阐述了ABPA的中西医结合治疗策略，西医以糖皮质激素和抗真菌药物为基础，生物制剂如奥马珠单抗为新兴选择，中医则通过辨证论治如风邪袭肺、痰瘀互结等证型联合中成药及针灸等特色疗法协同增效，以期为临床提供规范化指导。.
Anti-interferon-γ autoantibodies (AIGAs) are an established cause of adult-onset immunodeficiency (AOID), predisposing individuals to disseminated intracellular infections such as Talaromyces marneffei (TM). However, their role in promoting persistent immune dysregulation and subsequent lymphomagenesis remains poorly understood. A 63-year-old Chinese female with high-titer AIGAs (1:2500) initially presented with disseminated TM. Despite antifungal therapy, her clinical course was complicated by recurrent opportunistic infections-including Varicella-zoster virus (VZV) and Mycobacterium persicum (M. persicum), and steroid-dependent inflammatory episodes. Approximately two years after the initial presentation, she developed an Epstein-Barr virus (EBV)-positive aggressive B-cell lymphoma, confirmed by mass biopsy and PET/CT. Despite treatment with rituximab and broad-spectrum antimicrobials, she died of Gram-negative septic shock. Whole-exome sequencing (WES) revealed a CREBBP p.Q278P mutation, providing a genetic perspective on her disease susceptibility. This case illustrates a rare progression from AIGAs-associated immunodeficiency to EBV-driven lymphoma, suggesting a "triple-hit" pathogenic model that warrants further investigation, comprising: (1) AIGAs-associated AOID; (2) chronic antigenic stimulation from persistent infections that may exacerbate immune dysregulation; and (3) a CREBBP mutation that may act as a genetic contributor to malignant transformation. This case underscores the necessity for rigorous tumor surveillance and individualized treatment in patients with AIGAs-associated immunodeficiency.
The domesticated silkworm (Bombyx mori) is an established model for investigating pesticide ecotoxicology in Lepidoptera. However, a systems-level integration of its molecular response networks across diverse pesticide classes is still lacking. This review synthesizes multi-omics, physiological, and biochemical data to construct a comprehensive framework for the toxicity of B. mori. Our analysis revealed that pesticide exposure universally disrupts energy homeostasis by inhibiting mitochondrial oxidative phosphorylation (OXPHOS) and dysregulating trehalose metabolism, culminating in severe ATP depletion. The resulting overproduction of ROS sequentially triggers major defense pathways, such as the PI3K/Akt, MAPK/CREB, and CncC/Keap1 pathways. These pathways coordinate the transcriptional activation of antioxidant enzymes and detoxification proteins, including P450s, GSTs, and CarEs, via ARE- and XRE-dependent mechanisms. Concurrently, pesticides induce autophagy-apoptosis crosstalk via calcium dysregulation and caspase cascade activation. This molecular disruption is compounded by the reshaping of the gut microbiota, characterized by the enrichment of opportunistic pathogens, such as Enterobacter, and the depletion of beneficial symbionts, such as Bifidobacterium, alongside the suppression of Toll/IMD/JAK-STAT immune signaling. This dual assault on immunity and metabolism creates a synergistic 'multi-hit' effect that dramatically increases susceptibility to pathogens, such as BmNPV. This integrated framework identifies the CncC-ARE axis, mitochondrial energy sensors, and gut microbiota-host interactions as central regulatory hubs and promising targets for intervention. By translating these mechanistic insights from silkworms to broader lepidopteran pests, this study provides a theoretical foundation for ecological risk assessment and biomarker discovery. Furthermore, it establishes a roadmap for developing targeted green pest management strategies with direct implications for advancing sustainable sericulture and precision pest control. © 2026 Society of Chemical Industry.
Increasing incidence of candidiasis and emergence of antifungal resistance necessitate the development of alternative antifungal strategies. In this context, the antifungal activity of the crude extract of Punica granatum L. peel (PGPE) and its chitosan nanoparticle-coated formulation (PGPE-CSNPs) was investigated against Candida albicans (ATCC 10231), Candida glabrata (ATCC 66032), Candida kefyr (ATCC 46764), Candida parapsilosis (ATCC 22019), and Candida tropicalis (ATCC 13803). Although the individual antimicrobial activities of PGPE and CSNPs have been investigated, their combined application against Candida spp. remains unexplored in the literature. The antifungal efficacy was evaluated using agar well diffusion, disk diffusion, minimum inhibitory concentration (MIC), and minimum fungicidal concentration (MFC) testing, and compared with fluconazole and amphotericin B. The morphological characterization of PGPE-CSNPs was performed using scanning electron microscopy (SEM), which confirmed successful encapsulation and revealed a smoother surface with uniformly distributed nanometric pore structures and reduced aggregation compared to uncoated CSNPs. PGPE-CSNPs showed greater inhibition zones than amphotericin B, except against C. albicans. The CSNPs formulation reduced the MIC from 8 µg/mL to 4 µg/mL and the MFC from 16 µg/mL to 8 µg/mL, representing a two-fold enhancement against C. albicans. No enhancement in activity was observed against C. glabrata, whereas for C. kefyr, only MFC values decreased from 8 µg/mL to 4 µg/mL. For both C. parapsilosis and C. tropicalis, MIC values reduced from 16 µg/mL to 8 µg/mL, and MFC values reduced from 32 µg/mL to 16 µg/mL for both species. PGPE-CSNPs exhibited significantly lower MIC and MFC values than the crude extract alone (p < 0.05). These findings suggest that chitosan-based nanocarriers may enhance the antifungal efficacy of plant-derived bioactive compounds, highlighting their potential as a promising alternative antifungal strategy, a combinatorial approach not previously reported in the literature.
Immune reconstitution inflammatory syndrome (IRIS) refers to an exaggerated inflammatory response to existing infections or latent pathogens that occurs during rapid immune recovery in immunocompromised hosts, paradoxically leading to clinical deterioration despite appropriate treatment. IRIS is commonly observed in patients with human immunodeficiency virus (HIV)-associated tuberculosis and cryptococcal meningitis after starting antiretroviral therapy. However, it can also occur in immunocompromised individuals without HIV, which remains relatively under-recognized, particularly following neutrophil recovery after chemotherapy for acute leukemia or hematopoietic stem cell transplantation, during the post-operative phase of anti-rejection therapy following solid organ transplantation, or after the rapid reduction or withdrawal of corticosteroids or immunosuppressants, etc. This article summarizes the definition, clinical characteristics, diagnosis, treatment, and prevention of IRIS associated with invasive pulmonary fungal diseases. Clinical management requires accurate identification and careful evaluation to guide optimal and prompt intervention. Appropriate timing of antifungal treatment, initiation of antiretroviral therapy, and adjustment of immunosuppressive agents are crucial to reduce the risk of IRIS and prevent related morbidity and mortality. 免疫重建炎症反应综合征（IRIS）好发于HIV相关结核病、隐球菌脑膜炎患者ART治疗期，但近年来发现，IRIS同样好发于非HIV真菌感染患者免疫功能快速恢复期，如急性白血病化疗或造血干细胞移植患者粒细胞缺乏恢复期、实体器官移植术后抗排异治疗期、糖皮质激素等免疫抑制剂的快速减量或停用时，但临床对其认识相对不足。本文聚焦于侵袭性肺真菌病相关IRIS的定义、临床特征、诊断标准、治疗和预防，旨在为该病的早期识别和规范管理提供参考。.
Invasive fungal diseases are life-threatening complications, particularly in immunocompromised patients, and require rapid and accurate diagnosis to improve clinical outcomes. Although major advances in fungal diagnostics that includes antigen detection, molecular assays, and MALDI-TOF mass spectrometry, have transformed diagnostic strategies, access to these tools remains heterogeneous. In France, national data on diagnostic capacities for invasive fungal diseases have been lacking. Using the framework of the national prospective surveillance program for invasive fungal diseases (SINFONI network), we conducted a survey to assess laboratory diagnostic practices in France. A secured 116-item questionnaire was distributed to 58 participating laboratories, of which 48 responded (83%). Automated blood culture systems and MALDI-TOF mass spectrometry for yeast identification were universally available, with 40 (83%) of the 48 participating laboratories also using MALDI-TOF for mold identification. Antifungal susceptibility testing was performed on-site in 47 (98%) centres for yeasts and in 37 (77%) for molds. Antigen-based biomarkers were widely available on-site, particularly cryptococcal antigen (n=43, 90%) and Aspergillus galactomannan (n=39, 81%), whereas β-D-glucan testing was available in only 26 (54%) of the centres. PCR-based diagnostics were implemented on-site in 43 (88%) centres, most commonly for Pneumocystis jirovecii, Aspergillus spp., and Mucorales. Systematic screening for Candidozyma auris colonization in at-risk patients was performed in 30 (63%) centres, predominantly using culture-based methods (n=24). Overall, this survey provides the first national overview of diagnostic capacities for invasive fungal diseases in France, highlighting a strong laboratory mycology infrastructure while identifying remaining gaps in access to specific biomarkers, molecular assays, and mold antifungal susceptibility testing. Serious fungal infections can be life-threatening and require rapid diagnosis. A national survey of French hospital laboratories shows strong diagnostic capacity overall, but also reveals unequal access to some fungal biomarkers, molecular tests, and antifungal testing for moulds.
Heart transplantation faces a persistent donor shortage; therefore, hearts from donation after circulatory death have become a feasible option despite unavoidable warm ischemia and subsequent ischemia-reperfusion injury. Biliverdin, an endogenous bile pigment with strong antioxidant and anti-inflammatory properties, has shown protective effects against ischemia-reperfusion injury in several organ transplantation models. Whether biliverdin attenuates warm ischemic injury in donation after circulatory death heart transplantation remains unclear. This study evaluated biliverdin supplementation in the perfusate and preservation solution in a rat donation after circulatory death model. Circulatory death was induced under deep anesthesia, and warm ischemia was maintained for 18 minutes, including the mandatory 5-minute stand-off period. Donor hearts were then flushed and subsequently cold-stored in the same biliverdin-supplemented extracellular-type trehalose-containing Kyoto solution, whereas control grafts received extracellular-type trehalose-containing Kyoto without biliverdin at both stages before heterotopic transplantation. Grafts were assessed at 3 and 24 hours after reperfusion (n = 6 per group). Evaluations included early graft recovery, myocardial injury markers, histological and ultrastructural changes, and inflammatory and stress-response gene expression. Biliverdin significantly improved early graft recovery, shortening reanimation time and increasing left ventricular fractional shortening at 24 hours. Serum troponin I levels were lower in biliverdin-treated grafts. Biliverdin also reduced histological injury and inflammatory cell infiltration. Ultrastructural analysis showed preserved mitochondrial architecture and ultrastructural integrity. Early proinflammatory gene expression was suppressed. Biliverdin supplementation in the perfusate and preservation solution attenuates ischemia-reperfusion injury in the experimental rat donation after circulatory death heart transplantation model. These findings provide proof of concept for further mechanistic and translational evaluation of biliverdin for myocardial protection in donation after circulatory death.
Sugars are essential nutrients for the growth, development, and reproduction of insects. To enhance the reproductive and pest control potential of Trichogramma pintoi, this study investigated the effects of supplementing different concentrations (10%, 15%, 20%, and 25%) of nutrients, sucrose, glucose, fructose, maltose, trehalose, honey, and water (control), on the longevity, fecundity, flight capacity, and gustatory response of T. pintoi adults. The results showed that T. pintoi took the shortest time to locate 20% concentrations of the different nutrients and exhibited the longest feeding duration. Supplementing fructose (female 19.53 d, male 11 d) and sucrose (female 17.67 d, male 9 d) resulted in the longest adult longevity of T. pintoi, with the highest fecundity (131.73 eggs/female, and 137.4 eggs/female, respectively). While, T. pintoi fed on water had a shortest longevity (Female: 1.47 d, Male: 1.27 d), and a lowest fecundity (12.93 eggs/female). Additionally, supplementing with different sugar solutions significantly enhanced the flight capability of T. pintoi. Among them, honey produced the highest proportion of L4 (flight capability with Level 4), reaching 78.67%. This study demonstrated that supplementing with 20% fructose and sucrose can significantly prolong the longevity and fecundity of T. pintoi, while honey can significantly enhance their flight capacity. These findings provide a reference standard for improving the mass rearing capacity and application effcacy of T. pintoi pest control.
Infectious interface keratitis is an uncommon but potentially vision threatening complication of lamellar corneal surgery. While it has been described after deeper lamellar procedures, its occurrence following superficial anterior lamellar keratectomy (SALK) is exceedingly rare. To the best of our knowledge, such cases following limbal dermoid excision have not been previously reported. We describe two pediatric cases of fungal interface keratitis following SALK for limbal dermoids. Two children, a 12-year-old girl with Goldenhar syndrome and a 6-year-old boy with isolated limbal dermoids, underwent SALK for dermoid excision. Both had an uneventful early postoperative course. At 5 weeks and 4 weeks respectively, they developed graft infiltration with interface involvement. Initial microbiological evaluation was non-contributory, and both cases showed poor response to intensive topical antibacterial therapy. Due to progressive interface infiltrates, graft removal was performed. Microbiological analysis of explanted graft and host bed samples revealed fungal filaments, with culture confirming Aspergillus niger in both cases. Targeted antifungal therapy was initiated with topical natamycin and voriconazole, resulting in resolution of infection. Final visual acuity improved from 6/36 to 6/18 in the first case and from 6/18 to 6/9 in the second case, with no recurrence during follow up. Fungal interface keratitis can occur following SALK, although rare, and may present with delayed onset and poor response to antibacterial therapy. Early suspicion and timely graft removal are critical for diagnosis and management. Prompt initiation of antifungal therapy can lead to favorable anatomical and visual outcomes.
Corymbia citriodora wood holds extensive application value; however, due to the cross-pollination nature of C. citriodora and the significant genetic variation among offspring, a phenomenon is observed in plantations where trees with the same parental lineage exhibit varying diameter at breast height (DBH). In this study, we hypothesized that the observed DBH variation reflects two divergent adaptation strategies under winter conditions: smaller trees may exhibit heightened cold sensitivity, activating stress responses and entering early dormancy, whereas larger trees may sustain cambial activity through coordinated regulation of cell-cycle genes and carbohydrate metabolism. Metabolomics showed large trees enriched in phenolic compounds like picroside I and orientin. Transcriptomics revealed their genes were enriched in cell cycle and phenylalanine/tyrosine metabolism pathways, whereas small trees were enriched in abscisic acid (ABA) pathways. Integrated analysis revealed three patterns of transcript-metabolite coordination: (i) concordant upregulation (e.g., shikimate dehydrogenase (SDH)-shikimic acid), (ii) discordant regulation suggesting post-transcriptional control (raffinose accumulation without raffinose synthase (RFS) upregulation in small trees), and (iii) pathway-level flux redirection (phenylpropanoid pathway). Systematically, during winter, small trees exhibited stress-sensitive signatures, characterized by 9-cis-epoxycarotenoid dioxygenase (NCED), pyrabactin resistance/pyrabactin resistance-like (PYR/PYL), ABA-responsive element binding factor (ABF) upregulation, accumulation of raffinose, and transcriptional shift toward lignification (cinnamyl-alcohol dehydrogenase (CAD), peroxidase upregulation). Conversely, large trees showed molecular profiles indicative of stronger adaptability, with transcriptional signatures consistent with continued cell division (E2F transcription factor 3 (E2F3), mini-chromosome maintenance (MCM2/4/5/6) upregulation), cytoskeletal organization (kinesin KIN12B), and active carbohydrate metabolism (sucrose synthase (SUS), trehalose-6-phosphate phosphatase (TPP), alpha-amylase (AMY) upregulation), accumulating cinnamate and shikimic acid. This study advances understanding of tree growth variation by demonstrating that winter conditions reveal divergent adaptation strategies linked to DBH. The key conceptual advance is the integration of stress signaling, carbon metabolism, and cell-wall regulation into a unified framework where differential dormancy timing explains within-family growth variation. Large trees maintain a permissive growth state through coordinated upregulation of cell-cycle, cytoskeletal, and biosynthetic genes, while small trees exhibit coordinated stress responses that accelerate dormancy. These findings provide species-specific targets for functional validation-including E2F3, KIN12B, and NCED-and suggest that breeding for sustained winter cambial activity could enhance biomass production in subtropical plantations.
Trehalase, the primary enzyme responsible for the degradation of gastrointestinal trehalose ("mushroom sugar"), is well-characterised in the human gut, but has not been conclusively identified in the human brain. Trehalose itself has shown promise in neuroprotection through diverse molecular mechanisms, including the autophagy-driven clearance of cellular debris and neurotoxic aggregates. However, the mechanisms activating trehalose and its integration into human central nervous system processes remain elusive. To investigate the modulatory role of trehalase in the trehalose-mediated neuroprotection, we analysed two independent RNA-seq datasets derived from post-mortem human brain tissue. Hypothesis testing of age- and multiple sclerosis-associated changes in trehalase gene expression revealed significant decrease in both aged donors and patients with multiple sclerosis compared to controls. Differential gene correlation analysis combined with pathway enrichment showed that trehalase-associated gene networks shift according to bimodal age segmentation, implicating pathways related to autophagy, mitophagy, oxidative phosphorylation, and neurodegeneration. Moreover, trehalase expression correlated positively with oligodendrocyte proportions in many brain regions and negatively with neuronal proportions in the hippocampus, suggesting cell-type-specificity. A robust positive association with sirtuin 1 expression further links trehalase to established neuroprotection. These results provide the first direct evidence of trehalase expression in the human brain and suggest that the trehalase-trehalose axis may function as a mediator of cellular homeostasis and neuroprotection in neurons and glia. Our results position trehalase as a candidate biomarker and modulator of trehalose-linked pathways in ageing and neurodegeneration, warranting future studies integrating both trehalase and trehalose profiling in paired samples.
Off-flavor compounds often bind to proteins during extraction from animal byproducts and compromise protein applicability. This study proposed the integration of ultra-high pressure (UHP) pretreatment with propylene glycol and trehalose addition (UNPA) to facilitate off-flavor dissociation during duck liver protein (DLvP) extraction. UHP treatment at 350 MPa for 10 min induced a molten globule-like state with loosened tertiary packing and increased hydrophobic exposure, whereas propylene glycol and trehalose helped maintain the pressure-modulated conformation and limit aggregation. UNPA decreased the total peak area of headspace volatiles by approximately 50.8%, and reduced trimethylamine, dimethylamine, histamine, and formaldehyde by 28.78%, 32.19%, 12.21%, and 44.00%, respectively (p < 0.05). Water-holding capacity and emulsifying activity were improved by 13.6% and 60.1%, respectively (p < 0.05). These findings indicate that controlled UHP-induced unfolding, assisted by conformational stabilization, can promote off-flavor release while improving selected functional properties of DLvP.
Metamizole is an analgesic drug with moderate cytochrome P450 (CYP) inductive properties. The antifungal triazoles are metabolized by several CYP enzymes, but the interaction with metamizole remains poorly described. We investigated the influence of metamizole on the exposure of voriconazole, isavuconazole, and posaconazole. Patients from UZ Leuven (Belgium) and Ljubljana University Medical Centre (Slovenia) receiving voriconazole, isavuconazole, or posaconazole concomitantly with metamizole were included in the study. Routine therapeutic drug monitoring (TDM) measurements collected between January 2019 and December 2024 were retrieved retrospectively. TDM concentrations outside of concomitant therapy were collected as controls. The influence of metamizole and other clinically relevant covariates was analysed using generalized estimating equations (GEE). A total of 126 distinct treatments with a triazole from 115 patients, accounting for 392 measurements, were included in the study. GEE analysis revealed a significant negative association between the 7-day cumulative metamizole dose and lower voriconazole and posaconazole concentrations. Additionally, C-reactive protein had a positive association with voriconazole concentrations. Only ICU admission and patient characteristics, that is, sex and weight, had a significant influence on isavuconazole concentrations. Concomitant therapy with metamizole led to lower voriconazole and posaconazole concentrations, presumably through induction of CYP enzymes and possibly UDP-glucuronyltransferase. We recommend avoiding concomitant use of metamizole with the antifungal triazoles to prevent underexposure and treatment failure or frequent TDM if the combination cannot be avoided. Further studies are needed to confirm our findings and investigate the influence of metamizole on other triazoles.