RESUMO

Tuojiang River Basin is a first-class tributary of the upper reaches of the Yangtze River-which is the longest river in China. As phytoplankton are sensitive indicators of trophic changes in water bodies, characterizing phytoplankton communities and their growth influencing factors in polluted urban rivers can provide new ideas for pollution control. Here, we used direct microscopic count and environmental DNA (eDNA) metabarcoding methods to investigate phytoplankton community structure in Tuojiang River Basin (Chengdu, Sichuan Province, China). The association between phytoplankton community structure and water environmental factors was evaluated by Mantel analysis. Additional environmental monitoring data were used to pinpoint major factors that influenced phytoplankton growth based on structural equation modeling. At the phylum level, the dominant phytoplankton taxa identified by the conventional microscopic method mainly belonged to Bacillariophyta, Chlorophyta, and Cyanophyta, in contrast with Chlorophyta, Dinophyceae, and Bacillariophyta identified by eDNA metabarcoding. In α-diversity analysis, eDNA metabarcoding detected greater species diversity and achieved higher precision than the microscopic method. Phytoplankton growth was largely limited by phosphorus based on the nitrogen-to-phosphorus ratios > 16:1 in all water samples. Redundancy analysis and structural equation modeling also confirmed that the nitrogen-to-phosphorus ratio was the principal factor influencing phytoplankton growth. The results could be useful for implementing comprehensive management of the river basin environment. It is recommended to control the discharge of point- and surface-source pollutants and the concentration of dissolved oxygen in areas with excessive nutrients (e.g., Jianyang-Ziyang). Algae monitoring techniques and removal strategies should be improved in 201 Hospital, Hongrihe Bridge and Colmar Town areas.

Assuntos

Monitoramento Ambiental , Fitoplâncton , Rios , Rios/química , China , Poluentes Químicos da Água/análise , Fósforo/análise

RESUMO

Tamaricaceae comprises about 120 species and has a long evolutionary history, Tamarix Linn accounts for approximately 75% of the total species in this family. It is the most widely distributed and diverse genus in the family. They have important ecological significance for transforming deserts and improving climate conditions. However, Tamarix is the most poorly classified genera among flowering plants owing to its large variability and high susceptibility to interspecific hybridization. In this study, the complete chloroplast genomes of three Tamarix species and one draft chloroplast genome were obtained in this study. Combined with eight chloroplast genomes deposited in GenBank, complete chloroplast sequences of 12 Tamarix species were used for further analysis. There are 176 non-SSR-related indels and 681 non-indel-related SSRs in the 12 Tamarix chloroplast genomes. The mononucleotide SSRs are the most prevalent among all types of SSRs. The mVISTA results indicate high sequence similarities across the chloroplast genome, suggesting that the chloroplast genomes are highly conserved, except for sample Tamarix androssowii (ENC850343). The IR regions and the coding regions are more conserved than the single-copy and noncoding regions. The trnF-ndhJ, ndhC-trnM-CAU, ycf1, and trnL-UAG-ndhF regions are the most variable and have higher variability than those of the universal DNA markers. Finally, the first phylogenetic tree of Tamaricaceae was constructed which confirmed the monophyly of Tamarix in Tamaricaceae. The first phylogenetic tree of Tamarix was based on the complete chloroplast genome to date, the changes in branch length and support rate can potentially help us clarify the phylogenetic relationships of Tamarix. All the obtained genetic resources will facilitate future studies in population genetics, species identification, and conservation biology of Tamarix.

RESUMO

Actin stabilizers that are capable of interfering with actin cytoskeleton dynamics play an important role in chemical biology. Rhizopodin, a novel actin stabilizer, affects the actin cytoskeleton at nanomolar concentrations and exhibits potent antiproliferative activities against a range of tumor cell lines with IC50 values in the low nanomolar range. Herein, we report the total synthesis of rhizopodin based on a late-stage oxazole ring formation strategy, whose success demonstrates the feasibility of late-stage oxazole ring formation in the synthesis of complex oxazole containing natural products. Other features of the synthesis include a Nagao aldol reaction, a Suzuki coupling, a Yamaguchi esterification, a modified Robinson-Gabriel synthesis of the oxazoles, and a bidirectional Ba(OH)2-mediated Horner-Wadsworth-Emmons (HWE) reaction.

RESUMO

Background: Microangiogenesis and lymphangiogenesis are essential for tumor growth in the tumor microenvironment, contributing to tumor invasion and metastasis. Limited literature exists on these processes in esophageal squamous cell carcinoma (ESCC). Therefore, the purpose of this study is to explore the impacts of microangiogenesis and lymphangiogenesis on the occurrence, progression, and prognosis assessment of ESCC. Methods: Surgical specimens and paraffin-embedded human tissues were procured from ESCC patients, encompassing 100 ESCC tissues and 100 cancer-adjacent normal (CAN) tissues. CD34 and D2-40 were utilized as markers for microvessel endothelial cells and lymphatic vessel endothelial cells, respectively. Microvascular density (MVD) and lymphatic vessel density (LVD) were evaluated through immunohistochemical quantification. Results: We found that tumor tissues in ESCC patients had significantly higher MVD and LVD than cancer-adjacent normal (CAN) tissues. High MVD and LVD were associated with lymph node metastasis and advanced tumor clinical stages. Additionally, both high MVD and high LVD were strongly linked to poorer prognosis among cancer patients. Furthermore, a positive correlation was found between high MVD and high LVD (p < 0.05). The presence of these markers individually indicated a worse prognosis, with their combined assessment showcasing enhanced prognostic value. Conclusions: Overall, the increased MVD and LVD indicates higher invasion and metastasis of ESCC, closely correlating with unfavorablefor poor prognosis of ESCC patients.

Assuntos

Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Vasos Linfáticos , Densidade Microvascular , Humanos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/irrigação sanguínea , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Vasos Linfáticos/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/irrigação sanguínea , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/irrigação sanguínea , Metástase Linfática/patologia , Linfangiogênese/fisiologia , Idoso , Neovascularização Patológica/patologia , Microvasos/patologia , Antígenos CD34/metabolismo , Imuno-Histoquímica

RESUMO

BACKGROUND: Spinal cord stimulation can be considered in PHN patients if conservative treatment is not effective. However, the long-term pain outcomes of temporary (7-14 days) spinal cord stimulation (tSCS) in refractory PHN patients with a course of more than 3 months have not been  documented. OBJECTIVES: To investigate the efficacy of tSCS as a treatment for refractory PHN. STUDY DESIGN: Retrospective study. SETTING: Pain Department in a university hospital. METHODS: A total of 52 patients with refractory PHN were treated with tSCS between March 2018 and February 2021. Their medical records were collected, and the patients were divided into 3 groups according to the course of their disease into the medium-term group, long-term group and ultra-long-term group. The changes in the numeric rating scale (NRS) scores, Pittsburgh sleep quality index (PSQI) responses, pain relief rate, postoperative efficiency and patients' use of analgesics were recorded before the operation, 3 days, 10 days, one month, 3 months, 6 months and 12 months after the operation. RESULTS: The average NRS scores, the maximum NRS scores and the PSQI scores at 3 days, 10 days, one month, 3 months, 6 months and 12 months after the operation were significantly lower than those before the operation (P < 0.05). The average NRS scores and the maximum NRS scores of all groups increased significantly from one month to 6 months compared to those at 10 days after the tSCS treatment, and they decreased significantly at 12 months compared with 6 months post-operation. The average NRS scores of the medium-term and long-term group were significantly lower than that of the ultra-long-term group at 1-3 months after the operation, and the maximum NRS scores at one month, 3 months and 12 months after the operation were also significantly lower in the medium-term and long-term group compared to the ultra-long-term group. The average PSQI scores at 1-12 months after the operation were not significantly higher than that at 10 days after the operation, but it decreased significantly at 12 months compared with 6 months after the operation. Among the 3 groups, the PSQI scores of the medium-term and long-term group were significantly lower than those of the ultra-long-term group at 6 months after the operation. The postoperative pain relief rate ranged from 41.51%-59.81%, and the total effective rate was 42.31%-69.23%, and there was no significant difference among the 3 groups. Some patients still needed analgesics at 12 months after the operation, but the number of patients who were taking medications post-operation was significantly lower than that before the operation. LIMITATIONS: This is a single-center retrospective study with the inability to completely control for variables. Additionally, the number of cases is small and the follow-up duration is short. CONCLUSION: tSCS can be used as a safe and effective method to relieve refractory PHN, and the curative effect is substantially higher in patients with a disease course of 3-12 months compared to that in patients with a course of more than 12 months.

Assuntos

Neuralgia Pós-Herpética , Estimulação da Medula Espinal , Humanos , Estimulação da Medula Espinal/métodos , Estudos Retrospectivos , Neuralgia Pós-Herpética/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Medição da Dor , Manejo da Dor/métodos

RESUMO

Eukaryotic cells depend on dynamic changes in shape to fulfill a wide range of cellular functions, maintain essential biological processes, and regulate cellular behavior. The single-celled, predatory ciliate Lacrymaria exhibits extraordinary dynamic shape-shifting using a flexible "neck" that can stretch 7-8 times the length of its body to capture prey. The molecular mechanism behind this morphological change remains a mystery. We have observed that when in an active state, Lacrymaria repeatedly extends and contracts its neck to enable 360-degree space search and prey capture. This remarkable morphological change involves a unique actin-myosin system rather than the Ca2+-dependent system found in other contractile ciliates. Two cytoskeletons are identified in the cortex of the Lacrymaria cell, namely the myoneme cytoskeleton and the microtubule cytoskeleton. The myoneme cytoskeleton is composed of centrin-myosin proteins, exhibiting distinct patterns between the neck and body, with their boundary seemingly associated with the position of the macronucleus. A novel giant protein forming a ladder-like structure was discovered as a component of the microtubule cytoskeleton. Thick centrin-myosin fibers are situated very close to the right side of the ladders in the neck but are far away from such structures in the body. This arrangement enables the decoupling of the neck and body. Plasmodium-like unconventional actin has been discovered in Lacrymaria, and this may form highly dynamic short filaments that could attach to the giant protein and myosin, facilitating coordination between the two cytoskeletons in the neck. In summary, this fascinating organism employs unconventional cytoskeletal components to accomplish its extraordinary dynamic shape-shifting.

RESUMO

Herein, we report a photoinduced 1,7-hydrosulfonylation of allylic ethers and amides via a sequential Pd-mediated 1,5-HAT process and Pd-catalyzed allylic nucleophilic attack of arylsulfonates. This rationally designed synthetic protocol allows for facile construction of a series of structurally novel allylic sulfonated scaffolds, and features mild conditions, cheap and readily available raw materials and functional group compatibility.

RESUMO

Monkeypox (Mpox) has emerged as a global threat since 2022. We reported 14 cases of Mpox in 10 people with HIV (PWH) and 4 people without HIV (PWoH), of whom 64.3% had sexually transmitted co-infections. Severe complications of Mpox and prolonged viral shedding might occur in both PWH and PWoH.

RESUMO

Drought induces dry hazards, including wildfire, and increased air pollution from wildfire may be a mechanism by which drought increases health risks. We examined whether the drought-wildfire pathway increases the risk of childhood stunting. We analyzed all geocoded children under five across 44 low- and middle-income countries (LMICs). We first conducted mixed-effect regressions to examine the three pairwise associations between standardized precipitation evapotranspiration index (SPEI), fire-sourced PM2.5, and childhood stunting. We then employed a causal mediation analysis to determine whether compounding drought-wildfire (cascading or co-occurring) events significantly impact the drought-stunting pathway. We found that each 1-unit decrease in SPEI exposure was associated with a 2.16% [95% confidence interval (CI): 0.79, 3.49%] increase in stunting risk and 0.57 (95% CI 0.55, 0.59%) µg/m3 increase in fire-sourced PM2.5. Additionally, each 1 µg/m3 increase in 24 month average fire-sourced PM2.5 was associated with an increased risk of 2.46% (95% CI: 2.16, 2.76%) in stunting. Drought-mediated fires accounted for 26.7% (95% CI: 14.5, 36.6%) of the linkage between SPEI and stunting. Our study revealed fire-sourced PM2.5 is a mediator in the drought-stunting pathway in LMICs. To protect child health under increasing drought conditions, personal interventions against wildfire should be considered to enhance climate resilience.

RESUMO

The accumulation and systemic propagation of senescent cells contributes to physiological aging and age-related pathology. However, which cell types are most susceptible to the aged milieu and could be responsible for the propagation of senescence has remained unclear. Here we found that physiologically aged bone marrow monocytes/macrophages (BMMs) propagate senescence to multiple tissues, through extracellular vesicles (EVs), and drive age-associated dysfunction in mice. We identified peroxisome proliferator-activated receptor α (PPARα) as a target of microRNAs within aged BMM-EVs that regulates downstream effects on senescence and age-related dysfunction. Demonstrating therapeutic potential, we report that treatment with the PPARα agonist fenofibrate effectively restores tissue homeostasis in aged mice. Suggesting conservation to humans, in a cohort study of 7,986 participants, we found that fenofibrate use is associated with a reduced risk of age-related chronic disease and higher life expectancy. Together, our findings establish that BMMs can propagate senescence to distant tissues and cause age-related dysfunction, and they provide supportive evidence for fenofibrate to extend healthy lifespan.

RESUMO

Argonaute (Ago) proteins are programmable nucleases found in all domains of life, playing a crucial role in biological processes like DNA/RNA interference and gene regulation. Mesophilic prokaryotic Agos (pAgos) have gained increasing research interest due to their broad range of potential applications, yet their molecular mechanisms remain poorly understood. Here, we present seven cryo-electron microscopy structures of Kurthia massiliensis Ago (KmAgo) in various states. These structures encompass the steps of apo-form, guide binding, target recognition, cleavage, and release, revealing that KmAgo employs a unique DDD catalytic triad, instead of a DEDD tetrad, for DNA target cleavage under 5'P-DNA guide conditions. Notably, the last catalytic residue, D713, is positioned outside the catalytic pocket in the absence of guide. After guide binding, D713 enters the catalytic pocket. In contrast, the corresponding catalytic residue in other Agos has been consistently located in the catalytic pocket. Moreover, we identified several sites exhibiting enhanced catalytic activity through alanine mutagenesis. These sites have the potential to serve as engineering targets for augmenting the catalytic efficiency of KmAgo. This structural analysis of KmAgo advances the understanding of the diversity of molecular mechanisms by Agos, offering insights for developing and optimizing mesophilic pAgos-based programmable DNA and RNA manipulation tools.

RESUMO

Urea electrosynthesis by coelectrolysis of NO3- and CO2 (UENC) holds enormous promise for sustainable urea production, while the efficient UENC process relies on the rational design of high-performance catalysts to facilitate the electrocatalytic C-N coupling efficiency and the hydrogenation reaction process. Herein, Fe single atoms supported on MoS2 (Fe1/MoS2) are developed as a highly effective and robust catalyst for UENC. Theoretical calculations and operando spectroscopic measurements reveal a tandem catalysis mechanism of the Fe1-S3 motif and MoS2-edge to jointly promote the UENC process, where the Fe1-S3 motif drives the early C-N coupling and subsequent *CO2NO2-to-*CO2NH2 step. The generated *CO2NH2 is then migrated from the Fe1-S3 motif to the nearby MoS2-edge, which facilitates the *CO2NH2 → *COOHNH2 step for urea formation. Noticeably, Fe1/MoS2 assembled in a flow cell reaches a maximum urea Faraday efficiency of 54.98% with a corresponding urea yield rate of 18.98 mmol h-1 g-1, performing at the top level among all of the UENC catalysts reported to date.

RESUMO

Despite the substantial evidence on the health effects of short-term exposure to ambient fine particles (PM2.5), including increasing studies focusing on those from wildland fire smoke, the impacts of long-term wildland fire smoke PM2.5 exposure remain unclear. We investigated the association between long-term exposure to wildland fire smoke PM2.5 and nonaccidental mortality and mortality from a wide range of specific causes in all 3,108 counties in the contiguous United States, 2007 to 2020. Controlling for nonsmoke PM2.5, air temperature, and unmeasured spatial and temporal confounders, we found a nonlinear association between 12-mo moving average concentration of smoke PM2.5 and monthly nonaccidental mortality rate. Relative to a month with the long-term smoke PM2.5 exposure below 0.1 µg/m3, nonaccidental mortality increased by 0.16 to 0.63 and 2.11 deaths per 100,000 people per month when the 12-mo moving average of PM2.5 concentration was of 0.1 to 5 and 5+ µg/m3, respectively. Cardiovascular, ischemic heart disease, digestive, endocrine, diabetes, mental, and chronic kidney disease mortality were all found to be associated with long-term wildland fire smoke PM2.5 exposure. Smoke PM2.5 contributed to approximately 11,415 nonaccidental deaths/y (95% CI: 6,754, 16,075) in the contiguous United States. Higher smoke PM2.5-related increases in mortality rates were found for people aged 65 and above. Positive interaction effects with extreme heat were also observed. Our study identified the detrimental effects of long-term exposure to wildland fire smoke PM2.5 on a wide range of mortality outcomes, underscoring the need for public health actions and communications that span the health risks of both short- and long-term exposure.

Assuntos

Exposição Ambiental , Material Particulado , Fumaça , Humanos , Estados Unidos/epidemiologia , Material Particulado/efeitos adversos , Material Particulado/análise , Fumaça/efeitos adversos , Fumaça/análise , Exposição Ambiental/efeitos adversos , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/efeitos adversos , Feminino , Masculino , Incêndios Florestais , Mortalidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Idoso

RESUMO

BACKGROUND: International Classification of Diseases codes are widely used to describe diagnosis information, but manual coding relies heavily on human interpretation, which can be expensive, time consuming, and prone to errors. With the transition from the International Classification of Diseases, Ninth Revision, to the International Classification of Diseases, Tenth Revision (ICD-10), the coding process has become more complex, highlighting the need for automated approaches to enhance coding efficiency and accuracy. Inaccurate coding can result in substantial financial losses for hospitals, and a precise assessment of outcomes generated by a natural language processing (NLP)-driven autocoding system thus assumes a critical role in safeguarding the accuracy of the Taiwan diagnosis related groups (Tw-DRGs). OBJECTIVE: This study aims to evaluate the feasibility of applying an International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), autocoding system that can automatically determine diagnoses and codes based on free-text discharge summaries to facilitate the assessment of Tw-DRGs, specifically principal diagnosis and major diagnostic categories (MDCs). METHODS: By using the patient discharge summaries from Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUCHH) from April 2019 to December 2020 as a reference data set we developed artificial intelligence (AI)-assisted ICD-10-CM coding systems based on deep learning models. We constructed a web-based user interface for the AI-assisted coding system and deployed the system to the workflow of the certified coding specialists (CCSs) of KMUCHH. The data used for the assessment of Tw-DRGs were manually curated by a CCS with the principal diagnosis and MDC was determined from discharge summaries collected at KMUCHH from February 2023 to April 2023. RESULTS: Both the reference data set and real hospital data were used to assess performance in determining ICD-10-CM coding, principal diagnosis, and MDC for Tw-DRGs. Among all methods, the GPT-2 (OpenAI)-based model achieved the highest F1-score, 0.667 (F1-score 0.851 for the top 50 codes), on the KMUCHH test set and a slightly lower F1-score, 0.621, in real hospital data. Cohen κ evaluation for the agreement of MDC between the models and the CCS revealed that the overall average κ value for GPT-2 (κ=0.714) was approximately 12.2 percentage points higher than that of the hierarchy attention network (κ=0.592). GPT-2 demonstrated superior agreement with the CCS across 6 categories of MDC, with an average κ value of approximately 0.869 (SD 0.033), underscoring the effectiveness of the developed AI-assisted coding system in supporting the work of CCSs. CONCLUSIONS: An NLP-driven AI-assisted coding system can assist CCSs in ICD-10-CM coding by offering coding references via a user interface, demonstrating the potential to reduce the manual workload and expedite Tw-DRG assessment. Consistency in performance affirmed the effectiveness of the system in supporting CCSs in ICD-10-CM coding and the judgment of Tw-DRGs.

Assuntos

Algoritmos , Classificação Internacional de Doenças , Processamento de Linguagem Natural , Humanos , Taiwan , Inteligência Artificial

RESUMO

Xi-Kun Yuan Pin-Shi Ni Zhen-Hao Yan Zhi Yu Zhuang-Zhi Wang Chen-Kai Zhang Fang-Hui Li Xiao-Ming Yu 1Sports Department, Nanjing University of Science and Technology ZiJin College, Nanjing, China, 2School of Sport Sciences, Nanjing Normal University, Nanjing, China, 3Shanghai Seventh People's Hospital, Shanghai, China To investigate the effects of life-long exercise (LLE) on age-related inflammatory cytokines, apoptosis, oxidative stress, ferroptosis markers, and the NRF2/KAEP 1/Klotho pathway in rats. Eight-month-old female Sprague-Dawley rats were divided into four groups: 1) LLE: 18-month LLE training starting at 8 months of age, 2) Old moderate-intensity continuous training (OMICT): 8 months of moderate-intensity continuous training starting at 18 months of age, 3) Adult sedentary (ASED): 8 month-old adult sedentary control group, and 4) Old sedentary (OSED): a 26-month-old sedentary control group. Hematoxylin eosin staining was performed to observe the pathological changes of kidney tissue injury in rats; Masson's staining to observe the deposition of collagen fibers in rat kidney tissues; and western blotting to detect the expression levels of IL-6, IL 1beta, p53, p21, TNF-alpha, GPX4, KAEP 1, NRF2, SLC7A11, and other proteins in kidney tissues. Results: Compared with the ASED group, the OSED group showed significant morphological changes in renal tubules and glomeruli, which were swollen and deformed, with a small number of inflammatory cells infiltrated in the tubules. Compared with the OSED group, the expression levels of inflammation-related proteins such as IL-1beta, IL-6, TNF alpha, and MMP3 were significantly lower in the LLE group. Quantitative immunofluorescence analysis and western blotting revealed that compared with the ASED group, KAEP 1 protein fluorescence intensity and protein expression levels were significantly enhanced, while Klotho and NRF2 protein fluorescence intensity and protein expression levels were reduced in the OSED group. Compared with the OSED group, KAEP 1 protein fluorescence intensity and protein expression levels were reduced in the LLE and OMICT groups. Klotho and KAEP 1 protein expression levels and immunofluorescence intensity were higher in the LLE group than in the OSED group. The expression levels of GPX4 and SLC7A11, two negative marker proteins associated with ferroptosis, were significantly higher in the LLE group than in the OSED group, while the expression of p53 a cellular senescence-associated protein that negatively regulates SLC7A11, and the downstream protein p21 were significantly decreased. LLE may ameliorated aging-induced oxidative stress, inflammatory response, apoptosis, and ferroptosis by regulating Klotho and synergistically activating the NRF2/KAEP 1 pathway. Keywords: Life-long exercise, Moderate intensity continuous training, Aging, Kidney tissue, Ferroptosis.

Assuntos

Apoptose , Ferroptose , Rim , Proteínas Klotho , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Condicionamento Físico Animal , Ratos Sprague-Dawley , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/fisiologia , Feminino , Apoptose/fisiologia , Ratos , Ferroptose/fisiologia , Rim/metabolismo , Rim/patologia , Condicionamento Físico Animal/fisiologia , Envelhecimento/metabolismo , Envelhecimento/patologia , Inflamação/metabolismo , Inflamação/patologia , Transdução de Sinais/fisiologia , Glucuronidase/metabolismo , Biomarcadores/metabolismo

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Yinhua Miyanling Tablet (YMT), a traditional Chinese medicine consisting of 10 herbs, has been widely used clinically to treat urinary tract infections (UTIs), however, its therapeutic mechanism is not fully understood. AIM OF THE STUDY: To investigate the mechanism of YMT in treating UTIs through network pharmacology, multi-omics and experimental validation. MATERIALS AND METHODS: Clinically, blood and urine samples from YMT-treated UTI patients were collected for transcriptomic and metabolomic analyses. Computationally, compounds that are related to YMT were obtained from the databases, relevant targets were identified, and UTI-related targets were analyzed to determine the core signaling pathways. Subsequently, an integrated approach combining multi-omics and network pharmacology assisted in identifying the key pathways underlying therapeutic effects of YMT on UTI. Finally, a mouse model of UTI was established using uropathogenic Escherichia coli (UPEC), and the therapeutic mechanism of YMT on UTI was validated by ELISA, qRT-PCR and Western blotting. RESULTS: After taking YMT, patients showed reduced levels of urinary bacteria, white blood cells, and serum inflammatory factors (CRP, IL-6 and TNF-α). Multi-omics analysis combined with network pharmacology demonstrated that YMT significantly inhibited the TLR/MAPK/NFκB signaling pathway. In vivo experiments confirmed that YMT attenuated UPEC-induced pathological changes in bladder structural, reduced the expression of bladder proteins (TLR4, MyD88, p-p38 MAPK and p-p65 NFκB), increased protein expression of IκB-α, and attenuated the release of inflammatory factors (TNF-α, IL-6 and IL-1ß) in mice. CONCLUSION: YMT is effective in treating UTI by down-regulating the TLR4/p38MAPK/p65NFκB pathway, thereby providing a scientific basis for its clinical application.

RESUMO

With the alarming rise of antibiotic-resistant bacteria, novel antibacterial substances are urgently needed for controlling and treating multidrug-resistant bacterial infections. Edwardsiella piscicida is an important zoonotic enteric pathogen, that can cause systemic hemorrhagic septicemia in fish. Carvacrol, a major terpene of oregano essential oil, has a wide range of antibacterial activities. This study aimed to analyze the effect of carvacrol on the growth and virulence of E. piscicida in vitro. The minimum inhibitory concentration (MIC) of carvacrol against E. piscicida was 125 µg/mL. The sub-inhibitory concentrations of carvacrol significantly decreased the biofilm formation of E. piscicida in a dose dependent manner, whereas increased the hemolytic activity with a negative correlation. The quantitative real-time PCR results showed that carvacrol at sub-MICs downregulated the expression of related virulence genes, including flagellum (fimA, fliC, flgN), hemolysins (ethA, ethB), quorum sensing systems (luxR, qseB), T3SS (esrB, esrC) and T6SS (evpB, evpC). Moreover, carvacrol (≤1/8 MIC) reduced the cytotoxicity, adherence and internalization activities of E. piscicida to the EPC cells. In vivo trial, the diet mixed with carvacrol increased the survival of zebrafish infected with E. piscicida. Overall, these findings suggested that carvacrol might be a promising therapeutic agent against E. piscicida infection in aquaculture.

RESUMO

Nanomaterials, with their small size, surface characteristics, and antibacterial properties, are extensively employed across environmental, energy, biomedical, agricultural, and other industries. This study examined the antibacterial efficacy of magnesium hydroxide (Mg(OH)2) nanoparticles (NPs) against sulfate-reducing bacteria (SRB) within sediments. The inhibitory effects of two types of Mg(OH)2 NPs with distinct particle sizes (20.3 and 29.6 nm) and concentrations (0-10.0 mg/mL) were examined under optimal treatment conditions. The antibacterial mechanisms of Mg(OH)2 NPs through direct contact and dissolution effects were determined. The results revealed a correlation between the concentration, particle size, and inhibitory activity, with the smallest NPs (20.3 nm) at the highest concentration (10.0 mg/mL) substantially reducing SRB counts from 8.77 ± 0.18 to 6.48 ± 0.13 log10 colony forming units/mL after 6 h treatment. Treatment with high concentrations of Mg(OH)2 NPs induced cellular damage, reduced intracellular lactate dehydrogenase activity, and elevated intracellular catalase activity and H2O2 content, suggesting that the contact effect of NPs stimulated SRB. This leads to oxidative stress response and structural damage to the cell membrane, which has emerged as the primary driver of the antibacterial action of Mg(OH)2 NPs. This study presents a novel nanomaterial that can inhibit and control SRB in natural sedimentary environments.

Assuntos

Antibacterianos , Sedimentos Geológicos , Hidróxido de Magnésio , Sulfatos , Hidróxido de Magnésio/química , Hidróxido de Magnésio/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Sedimentos Geológicos/microbiologia , Sulfatos/química , Sulfatos/farmacologia , Nanopartículas/química , Peróxido de Hidrogênio/farmacologia , Tamanho da Partícula , Bactérias/efeitos dos fármacos , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana

RESUMO

Sludge solubilization is known as a rate-limiting step of anaerobic digestion. Although radio frequency (RF) has been applied for sludge pretreatment due to its similar thermal effect as microwave, the potential non-thermal effects of RF treatment remain controversial. In this study, we demonstrate that RF pretreatment enhances the solubilization and lysis of sludge by 8.02%-19.69% through both thermal and non-thermal mechanisms with less energy input. Scanning electron microscope images provide direct evidence that RF-induced microcurrents penetrated bacterial cells, leading to the release of intracellular substances through formed pores. Additionally, the non-thermal effect of RF treatment which could weaken the cell protection and accelerate the lysis rate involves the disruption of binding forces between extracellular polymeric substances and microbial cells. On average, the utilization of RF at a frequency of 27.12 MHz demonstrates its efficacy as a sludge pretreatment technique, as evidenced by a 13.39% reduction in energy consumption and a 16.9% improvement in treatment performance compared to conductive heating (CH). The findings of this study elucidate the possible mechanism of RF treatment of sludge and could establish a theoretical basis for the practical application of RF treatment in sludge management.