Frontiers in Microbiology
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2022
·
IF 6.064
Guo Penghao,Chen Jianlong,Tan Yiwei,Xia Li,Zhang Weizheng,Li Xiaojie,Jiang Yujie,Li Ruiying,Chen Chunmei,Liao Kang,Peng Yaqin
Background: Fusarium species are opportunistic causative agents of superficial and disseminated human infections. Fast and accurate identification and targeted antifungal therapy give help to improve the patients’ prognosis.Objectives: This study aimed to evaluate the effectiveness of matrix-assisted laser desorption ionisation time of flight mass spectrometry (MALDI-TOF MS) for Fusarium identification, and investigate the epidemiology and antifungal susceptibility profiles of clinical Fusarium isolates in Southern China.Methods: There were 95 clinical Fusarium isolates identified by DNA sequencing of translation elongation factor 1-alpha (TEF1α) and MALDI-TOF MS, respectively. Antifungal susceptibility testing of isolates was performed by broth microdilution according to the CLSI approved standard M38-A3 document.Results: Seven species complexes (SC) with 17 Fusarium species were identified. The most prevalent SC was the F. solani SC (70.5%, 67/95), followed by the F. fujikuroi SC (16.8%, 16/95). F. keratoplasticum within the F. solani SC was the most prevalent species (32.6%, 31/95). There were 91.6% (87/95) of isolates identified by MALDI-TOF MS at the SC level. In most of species, amphotericin B and voriconazole showed lower MICs compared to itraconazole and terbinafine. The F. solani SC showed higher MICs to these antifungal agents compared to the other SCs. There were 10.5% (10/95) of strains with high MICs for amphotericin B (≥8 μg/ml), terbinafine (≥32 μg/ml) and itraconazole (≥32 μg/ml) simultaneously, mostly focusing on F. keratoplasticum (9/10).Conclusion: MALDI-TOF MS exhibited good performance on the identification of Fusarium strains at the SC level. The F. solani SC was the most prevalent clinical SC in Southern China. The MICs varied significantly among different species or SCs to different antifungal agents.
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JOURNAL OF MATERIALS SCIENCE
·
2020
·Vol. 55
·期 34
·16143-16157
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IF 3.553
Xu Lingling,Zhao Yajuan,Zhao Changhao,Hu Tao,Wang Jing,Liu Yi,Tian Yong,Wang Xiufang
Abstract Flower-like porous carbon has fascinated significant attention due to its outstanding and exceptional properties. However, controlled synthesis of porous carbon with adjustable morphology, highly active sites and cross-linked pore channels remains still a great challenge. Herein, an inimitable dissolution–reassembly anisotropic growth strategy was firstly demonstrated for the fabrication of idiographic orchid-like hierarchical porous carbon with ultra-thin multilayer carbon sheets, high specific surface area (1063 m 2 g −1 ), large pore volume (0.82 cm 3 g −1 ) and rich nitrogen content (7.6 wt%). Highly reactive phloroglucinol and EDA aggregated magically and SiO 2 acted as a pore former. Ingeniously, acetone acted as a “surgical knife,” which cut the composite of SiO 2 @phloroglucinol–EDA into many tiny units and further anisotropic growth into orchid-like polymers. The width and thickness of the carbon petals can be effectively controlled with the diversification of acetone concentration. Intriguingly, monodisperse hollow carbon nanospheres could be harvested with silicon-deficient system, which may offer new insight into the construction of functionalized carbon materials with hollow architecture. Owing to the unmatched superstructures, orchid-like carbon materials can be employed as an ideal drug carrier and dye adsorbent. Graphic abstract Figure Schematic illustration of solid carbon nanosphere, hollow carbon nanosphere and OHPC-25. For the first time, a novel dissolution–reassembly route based on strong hydrogen-bonding interaction was developed to prepare unique orchid-like hierarchical porous carbon, in which phloroglucinol acted as a carbon precursor and EDA both as a base catalyst and as a nitrogen precursor. The critical step to this synthetic approach was the ingeniously employed acetone as a “surgical knife” to cut the composite of SiO2@phloroglucinol–EDA into many tiny units, and these units were reassembled into orchid-like polymers. After adding acetone, the morphology of carbon materials has changed from solid nanospheres to hollow nanospheres. This strategy did not use any template as the cavity, which may offer a new insight into the comprehension of synthesized functionalized carbon materials with hollow architecture.
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ACS Applied Bio Materials
·
2019
·
IF 0
Lihua Zhou,Yayun Wu,Yuan Luo,Hongfeng Li,Xiaoqing Meng,Chuangjun Liu,Jingjing Xiang,Pengfei Zhang,Ping Gong,Lintao Cai
Recently, fluorescent dyes with a structure-inherent mitochondria-targeting capability have obtained great attention as single-molecule self-reporting theranostic agents to distinguish cancer cells from normal cells. However, there was little attempt using these dyes as a self-reporting ligand for cancer-targeted delivery of nanomaterials or drugs for personalized therapy. Herein, we developed a mitochondria-localized multifunctional nanodelivery system for cancer-targeted drug delivery and dual-modal imaging. First, a series of cyanine-structural small molecules with different-charged substituent groups have been screened based on their mitochondria targeting capability. Furthermore, the cyanine-structural molecule with the best mitochondria-targeting ability was decorated on iron oxide nanoparticles (IONP) for dual-modal imaging. The nanoprobes entered into the cancer cell via the organic anion transporting polypeptide (OATP) pathway and anchored on mitochondria due to the strong interaction between the negative mitochondria membrane and the lipophilic cationic cyanine dye. This work opened an avenue using small molecules with structure-inherent-targeting and self-reporting characteristics as a chemical ligand to develop cancer-targeting and subcellular-localized delivery system.
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JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Kaili Deng,Hailong Tian,Tingting Zhang,Yajie Gao,Edouard C. Nice,Canhua Huang,Na Xie,Guoliang Ye,Yuping Zhou
Colorectal cancer (CRC) is a prevalent clinical malignancy of the gastrointestinal system, and its clinical drug resistance is the leading cause of poor prognosis. Mechanistically, CRC cells possess a specific oxidative stress defense mechanism composed of a significant number of endogenous antioxidants, such as glutathione , to combat the damage produced by drug-induced excessive reactive oxygen species (ROS). We report on a new anti-CRC nanoplatform, a multifunctional chemo-photothermal nanoplatform based on Camptothecin (CPT) and IR820, an indocyanine dye. The implementation of a GSH-triggered ferroptosis-integrated tumor chemo-photothermal nanoplatform successfully addressed the poor targeting ability of CPT and IR820 while exhibiting significant growth inhibitory effects on CRC cells. Mechanistically, to offset the oxidative stress created by the broken Se Se bonds, endogenous GSH was continuously depleted, which inactivated GPX4 to accumulate lipid peroxides and induce ferroptosis . Concurrently, exogenously administered linoleic acid was oxidized under photothermal conditions, resulting in an increase in LPO accumulation. With the breakdown of the oxidative stress defense system, chemotherapeutic efficacy could be effectively enhanced. In combination with photoacoustic imaging, the nanoplatform could eradicate solid tumors by means of ferroptosis-sensitized chemotherapy. This study indicates that chemotherapy involving a ferroptosis mechanism is a viable method for the treatment of CRC.
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Microbiology Spectrum
·
2025
·
IF 3.8
Heng Zhang,Yizheng Zhou,Hanmo Yang,Xinyi Tao,Yinping Chen,Fuqiang Dong,Yi Sun
The growing resistance of Aspergillus to azoles poses a significant challenge in treating invasive fungal infections. This study aimed to investigate the synergistic effect of berbamine hydrochloride (BBM) combined with azoles in treating Aspergillus fumigatus and explore the role of efflux pump inhibition in this synergy. The efficacy of combining BBM with itraconazole (ITC), voriconazole (VOR), and posaconazole (POS) was tested against 69 A. fumigatus strains that had been identified using the M38-A3 broth microdilution method. quantitative reverse transcription PCR (RT-qPCR) was used to measure gene expression related to synergy, while flow cytometry was employed to assess mitochondrial reactive oxygen species (ROS) levels, and Rhodamine 6G exocytosis assays were performed to quantify efflux pump activity. BBM alone showed no significant antifungal activity. BBM combined with POS exhibited synergy against 66 strains (95.7%), while two clinical isolates (Af05/Af08) and one defective strain (Δcdr1B) showed no synergy. Synergy with ITC was observed in three strains (4.3%), but not with VOR. In the non-synergistic Af05 and Af08 strains, the expression of the cdr1B gene was significantly lower compared to wild-type (WT) strains. ROS levels increased significantly in WT with POS and BBM combination therapy, but not in the defective strains. Glucose uptake was also reduced in the POS-BBM combination. BBM enhances azole sensitivity in A. fumigatus primarily by inhibiting the cdr1B-mediated efflux pump, supported by reduced Rhodamine 6G exocytosis and synergy loss in cdr1B-deficient strains. ROS accumulation and metabolic disruption may further contribute to this synergy. Targeting efflux pumps with BBM provides a novel strategy to combat azole resistance.
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Frontiers in Microbiology
·
2025
·
IF 4.5
Mengmin Liang,Qingwen Hu,Junhao Yu,Heng Zhang,Sijie Liu,Jiangrong Huang,Yi Sun
Background: Invasive fungal infections (IFIs) constitute a significant health challenge, particularly among immunocompromised individuals, characterized by a high prevalence and associated mortality rates. The synergistic administration of Baicalein (BE) with azole antifungal agents could potentially herald a novel therapeutic paradigm.Materials and methods: 54 Aspergillus strains and 23 strains of dematiaceous fungi were selected. The standard M38-A2 microbroth dilution method was used to test the minimum inhibitory concentration (MIC) and the fractional inhibitory concentration index (FICI) of fungi when BE combined with itraconazole (ITC), voriconazole (VRC), posaconazole (POS) and Isavuconazole (ISV).Results: BE shows synergistic effects with POS and ITC, with 89.61% and 25.97% of fungal strains. The BE/POS regimen exerted synergistic effects in 87.04% of Aspergillus and an impressive 95.65% of dematiaceous fungi. In comparison, the BE/ITC combination showed significantly lower synergy, affecting 33.33% of Aspergillus and a mere 8.70% of dematiaceous strains. Antagonistic interactions were sporadically observed with BE in combination with ITC, VRC, POS and ISV. Within the azole class, the BE/POS pairing stood out for its frequent synergistic activity, in contrast to the absence of such effects when BE was paired with VRC or ISV. Highlighting the potential of BE/POS as a notably effective antifungal strategy.Conclusion: In vitro, BE/POS combination emerged as the most effective antifungal strategy, exhibiting synergistic effects in the majority of Aspergillus and dematiaceous fungi strains, whereas BE/ITC showed significantly less synergy, and BE with VRC or ISV displayed no synergistic activity.
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CRYSTAL GROWTH & DESIGN
·
2024
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IF 3.2
Shengzheng Guo,Yuechao Cao,Yuxin Zhang,Yan Wang,Zhenguo Gao,Junbo Gong
Inhaled drug delivery has garnered increasing attention due to its inherent advantages including rapid onset of action, targeted delivery, high bioavailability, and reduced side effects, which holds promise for the treatment of localized lung diseases and systemic diseases. The currently dominant technologies for the preparation of inhalants are air flow pulverization, media milling, and spray drying, which encounter challenges such as inaccurate particle size control, inefficiency, instability, and difficulties in scaling up. The present study proposes a freeze-dissolving technique (FDT) for the preparation of inhalable microcrystals, comprising two essential steps: rapid freezing of microdroplets into iced pellets within seconds and subsequent dissolution of a solvent in the iced pellets to release the microcrystals in a suspension. By employing the FDT technique, griseofulvin, a representative inhalant, was successfully engineered into a bipyramidal morphology with a targeted particle size (<5 μm), minimal agglomeration (<3%), and an aspect ratio below 2, in which the solvent and stabilizer systems played pivotal roles in facilitating or impeding nucleation and crystal growth processes. To verify the universality of the FDT, six other typical inhalant preparation processes were successfully developed based on the FDT with a controllable crystal size between 1 and 10 μm. Furthermore, three out of the aforementioned seven model substances were randomly selected, and their preparation was scaled up by a factor of 100, yielding consistent results with those obtained at a smaller test scale. This study outlines the freeze-dissolving mechanism in ultrafine crystal formation and demonstrates that the FDT is a robust and scalable approach for the production of inhalants.
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SEPARATION AND PURIFICATION TECHNOLOGY
·
2025
·
IF 9
Xiaoxiang Cheng,Zhe Xu,Xinsheng Luo,Yi Chai,Jiajian Xing,Xinyu Zhang,Jingtao Xu
Inorganic membranes are prime candidates for organic solvent recovery in the pharmaceutical industry due to their excellent solvent resistance, mechanical strength and durability. However, constructing high-performance inorganic separation layers is still the most challenging aspect in the fabrication of inorganic membranes for organic solvent nanofiltration (OSN). Prussian blue analogues (PBAs) exhibit high chemical stability for their rigid cubic framework with strong covalent metal-cyanide coordination bonds. Inspired by the interfacial polymerization (IP) strategy, this study proposes a simple synthesis method for prussian blue analog thin films (PBA TFs) on porous ceramic substrates, using coordination reactions between K 3 [Fe(CN) 6 ] and acetylacetonate (e.g. Cu(acac) 2 , Mn(acac) 3 or Co(acac) 2 ). The Mn-Fe PBA membrane exhibits high solvent permeance (e.g., 176.4 L·m −2 ·h −1 ·bar −1 for ethyl acetate) and demonstrates a molecular weight cut-off ranging from 665 to 760 Da across six tested solvents. To evaluate the industrial potential of Mn-Fe PBA membranes, solvent recovery experiments were conducted in a twin-stage OSN system using seven active pharmaceutical ingredient (API)/solvent systems. In the tylosin/dimethyl sulfoxide system, the Mn-Fe PBA membrane achieved over 80 % total API retention, maintaining stable performance across multiple cycles. The formation process of PBA TFs was analyzed by adjusting monomer diffusion conditions. Furthermore, molecular dynamics simulations elucidated the film formation mechanism. The self-limiting nature of the IP strategy not only inhibits the formation of PBA large crystals, but also induces the self-assembly of PBA nanocrystals along the n-hexane/water interface, resulting in a complete PBA TF. This IP strategy blazes a new trail for fabrication of high-performance inorganic OSN membranes.
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Microbiology Spectrum
·
2025
·Vol. 13
·期 8
·
IF 3.8
Tian Chen,Shaolan Liu,Fei Yang,Zhangxuan He,Menghua Tang,Lu Ge,Hongyi Zhang,Sijie Liu,Xiaolei Zhu,Mengqi Peng,Heng Zhang,Wenxu Cheng,Yi Sun
Invasive fungal infections and emerging antifungal resistance mediated by pathogenic fungi, notably Candida spp., Aspergillus spp., Cryptococcus neoformans, and Exophiala dermatitidis, pose a critical challenge to global public health systems. This study evaluated the synergistic antifungal activity of oleanolic acid (OA) combined with five azole agents (itraconazole [ITR], voriconazole [VOR], posaconazole [POS], isavuconazole [ISA], and fluconazole) against Candida spp., Aspergillus spp., E. dermatitidis, and C. neoformans. Using CLSI-compliant broth microdilution assays (M27-A3/M38-A2), we determined the minimum inhibitory concentrations (MICs) of oleanolic acid against four fungal pathogens and evaluated in vitro synergistic interactions with five azoles to assess their therapeutic potential. OA exhibited no intrinsic fungicidal activity when administered alone. However, synergistic inhibition was observed in specific azole combinations across tested pathogens: Candida spp. (n = 18) demonstrated 33% (6/18) and 56% (10/18) synergy rates with ITR and POS, respectively. Aspergillus spp. (n = 30) showed enhanced synergism at 80% (24/30) for ITR and 97% (29/30) for POS. All OA-azole combinations were synergistic against C. neoformans (n = 8), with rates of 75% (6/8) for ITR, 75% (6/8) for VOR, 87.5% (7/8) for ISA, and 100% (8/8) for POS. In contrast, E. dermatitidis (n = 21) responded only to OA/POS (52%, 11/21). Overall synergistic frequencies were POS (75%, 58/77) > ITR (47%, 36/77) > ISA (9%, 7/77) > VOR (8%, 6/77). The OA-azole combinations demonstrated significant reductions in azole MIC values and exhibited synergistic antifungal activity, particularly against Aspergillus spp. and C. neoformans. While the mechanistic basis of OA’s chemosensitization remains uncharacterized, its multi-target pharmacological profile underscores potential utility in combating antifungal resistance.
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Drug Design Development and Therapy
·
2025
·
IF 5.1
Cong Xie,Tongshu Guan,Jin Huang,Jiayu Chen,Yilei Li,Ping Zheng
Purpose Lorlatinib, a third-generation inhibitor of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1), undergoes extensive metabolism, with its disposition influenced by drug–drug interactions (DDIs). This study aimed to characterize its in vitro metabolism, in vivo pharmacokinetics (PK), tissue distribution, and the effects of cytochrome P450 3A4 (CYP3A4) modulation in rats.Methods Lorlatinib metabolism was investigated in human liver microsomes (HLM) and rat liver micro- somes (RLM) using ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) with selective CYP inhibitors. Pharmacokinetic (PK) studies were performed in Sprague–Dawley (SD) rats following oral and intravenous dosing, including coadministration with CYP3A4 inhibitors (voriconazole, itraconazole) and inducers (rifampicin, carbamazepine). Tissue distribution was assessed across major organs.Results In vitro assays confirmed CYP3A4 as the primary enzyme mediating lorlatinib metabolism, with distinct differences in kinetic parameters between HLM and RLM. In vivo, lorlatinib displayed nonlinear PK, low oral bioavailability (8.6%), and extensive first-pass metabolism. Voriconazole increased exposure [area under the curve from 0–24 h (AUC(0−24h))] by 120%, whereas rifampicin reduced it by 77%, demonstrating strong CYP3A4-dependent interactions. Lorlatinib distributed rapidly to highly perfused organs and achieved efficient brain penetration (brain-to-plasma ratio = 0.82).Conclusion Lorlatinib undergoes extensive CYP3A4-mediated metabolism, exhibits nonlinear PK, and shows poor oral bioavailability in rats. Significant interspecies differences between HLM and RLM emphasize the need for caution when translating preclinical findings. Coadministration with CYP3A4 modulators markedly altered systemic exposure, while effective brain penetration supports its therapeutic role in central nervous system (CNS) metastases.
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CRYSTENGCOMM
·
2025
·
IF 2.6
Yuxin Zhang,Guo Shengzheng,Zhenguo Gao,Junbo Gong
The enhancement of solubility or bioavailability can be achieved by stabilizing the metastable solid state or reducing particle size, particularly for pharmaceutical candidates classified under biopharmaceutics classification system (BCS) II. In this paper, the ultrafine powder of itraconazole (ITZ) in amorphous state was prepared by a novel preparation method, the freeze-dissolving technology (FDT). The influence of additives, solvent systems, and process parameters was comprehensively investigated on the particle size and solid state of the ITZ slurry suspension. The experiments were conducted to investigate the solubility and dissolution rate, revealing a more than six-fold increase in accumulated dissolution of the amorphous phase with reduced size. The enhanced dissolution performance of the drug is attributed to its reduced particle size and amorphous state. Moreover, the final ultrafine powder of ITZ meets the size requirements for inhalable particles (usually the particles must be in the size range 0.5 to 5 micron), making it a potential dry powder inhalant (DPI) preparation mechanism for treating pulmonary fungal infections.
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Antibiotics-Basel
·
2025
·Vol. 14
·期 5
·499
·
IF 4.6
Liyang Wang,Junying He,Hanzhong Feng,Qian Li,Meirong Song,Haoran Gou,Yongxing He,Kui Zhu
Background:Fungal infections pose an increasingly predominant threat to human and animal health. Modified compounds derived from chemo-diverse natural products offer enhanced therapeutic efficacies and promising approaches to combat life-threatening fungal pathogens.Methods:We performed biosynthetic gene clusters analysis of 2,4-diacetylchloroglucoside (DAPG) in 4292 shotgun metagenomes samples from the healthy and diseased skin. Then, we assessed the antifungal activity of DAPG and the derivative 2,4-diproylphloroglucinol (DPPG) against pathogenic fungi by minimum inhibitory concentrations. The inhibitory effects of DPPG were measured using hyphal growth assay and spore germination assay. Concurrently, the mechanism of DPPG onAspergillus fumigatuswas investigated in membrane permeability and fluidity. The therapeutic efficacy was evaluated in aGalleria mellonellainfection model.Results:We observed a significantly higher abundance of bacteria harboring DAPG biosynthetic clusters on healthy skin compared to diseased skin. Further, we designed and synthesized a series of phloroglucinol derivatives based on DAPG and obtained an antifungal candidate DPPG. DPPG not only exhibited robust antifungal activity againstAspergillusspp. andCandidaspp. but also impaired hyphal growth and spore germination ofA. fumigatusin vitro. A mechanism study showed that DPPG reduced membrane fluidity and increased the leakage of cellular contents, resulting in membrane perturbation and fungal death. Lastly, the therapeutic efficacy of DPPG was confirmed in aG. mellonellainfection model.Conclusions:Our study demonstrates that DPPG is a potent scaffold to combat invasive fungal infections.
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