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1.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(6): 863-869, 2024 Jun 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-39311782

RESUMO

Intracranial seminoma is a rare malignant tumor originating from the germ cells, usually occurring in the pineal gland or pituitary gland. In June 2020, the Department of Endocrinology at the First Affiliated Hospital of Army Military Medical University admitted a 20-year-old male patient with an intracranial germ cell tumor and spinal metastases. The patient presented with headache, dizziness, and visual impairment. Enhanced magnetic resonance imaging (MRI) of the head indicated thickening of the pituitary stalk. After multidisciplinary consultation, the patient underwent endonasal transsphenoidal resection of the tumor, with the pathological diagnosis confirming germ cell tumor. The patient received regular radiotherapy postoperatively. One year later, the tumor recurred and metastasized, leading to a second surgery for tumor resection in the thoracic spinal canal, followed by continued chemotherapy. The patient's clinical symptoms, such as headache and visual disturbances, improved, but he continued to experience panhypopituitarism and required long-term hormone replacement therapy. Early diagnosis of intracranial germ cell tumors is challenging, and they are prone to metastasis and highly sensitive to radiotherapy and chemotherapy. Early diagnosis and multidisciplinary comprehensive treatment can help improve the quality of life and prognosis for patients.


Assuntos
Imageamento por Ressonância Magnética , Seminoma , Humanos , Masculino , Seminoma/patologia , Adulto Jovem , Hipófise/patologia , Hipófise/diagnóstico por imagem , Hipopituitarismo/etiologia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Recidiva Local de Neoplasia , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/diagnóstico por imagem
2.
Nat Commun ; 15(1): 7803, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39242627

RESUMO

Phenomena of free-electron X-ray radiation are treated almost exclusively with classical electrodynamics, despite the intrinsic interaction being that of quantum electrodynamics. The lack of quantumness arises from the vast disparity between the electron energy and the much smaller photon energy, resulting in a small cross-section that makes quantum effects negligible. Here we identify a fundamentally distinct phenomenon of electron radiation that bypasses this energy disparity, and thus displays extremely strong quantum features. This phenomenon arises when free-electron transverse scattering occurs during the radiation process, creating entanglement between each transversely recoiled electron and the photons it emitted. This phenomenon profoundly modifies the characteristics of free-electron radiation mediated by crystals, compared to conventional classical analysis and even previous quantum analysis. We also analyze conditions to detect this phenomenon using low-emittance electron beams and high-resolution X-ray spectrometers. These quantum radiation features could guide the development of compact coherent X-ray sources facilitated by nanophotonics and quantum optics.

3.
Nat Cell Biol ; 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39251719

RESUMO

The ten-eleven translocation (TET) family of dioxygenases maintain stable local DNA demethylation during cell division and lineage specification. As the major catalytic product of TET enzymes, 5-hydroxymethylcytosine is selectively enriched at specific genomic regions, such as enhancers, in a tissue-dependent manner. However, the mechanisms underlying this selectivity remain unresolved. Here we unveil a low-complexity insert domain within TET2 that facilitates its biomolecular condensation with epigenetic modulators, such as UTX and MLL4. This co-condensation fosters a permissive chromatin environment for precise DNA demethylation. Disrupting low-complexity insert-mediated condensation alters the genomic binding of TET2 to cause promiscuous DNA demethylation and genome reorganization. These changes influence the expression of key genes implicated in leukaemogenesis to curtail leukaemia cell proliferation. Collectively, this study establishes the pivotal role of TET2 condensation in orchestrating precise DNA demethylation and gene transcription to support tumour cell growth.

4.
Elife ; 132024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39172036

RESUMO

Background: The associations of age at diagnosis of breast cancer with incident myocardial infarction (MI) and heart failure (HF) remain unexamined. Addressing this problem could promote understanding of the cardiovascular impact of breast cancer. Methods: Data were obtained from the UK Biobank. Information on the diagnosis of breast cancer, MI, and HF was collected at baseline and follow-ups (median = 12.8 years). The propensity score matching method and Cox proportional hazards models were employed. Results: A total of 251,277 female participants (mean age: 56.8 ± 8.0 years), of whom 16,241 had breast cancer, were included. Among breast cancer participants, younger age at diagnosis (per 10-year decrease) was significantly associated with elevated risks of MI (hazard ratio [HR] = 1.36, 95% confidence interval [CI] 1.19-1.56, p<0.001) and HF (HR = 1.31, 95% CI 1.18-1.46, p<0.001). After propensity score matching, breast cancer patients with younger diagnosis age had significantly higher risks of MI and HF than controls without breast cancer. Conclusions: Younger age at diagnosis of breast cancer was associated with higher risks of incident MI and HF, underscoring the necessity to pay additional attention to the cardiovascular health of breast cancer patients diagnosed at younger age to conduct timely interventions to attenuate the subsequent risks of incident cardiovascular diseases. Funding: This study was supported by grants from the National Natural Science Foundation of China (82373665 and 81974490), the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences (2021-RC330-001), and the 2022 China Medical Board-open competition research grant (22-466).


Assuntos
Neoplasias da Mama , Insuficiência Cardíaca , Infarto do Miocárdio , Humanos , Feminino , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/diagnóstico , Pessoa de Meia-Idade , Insuficiência Cardíaca/epidemiologia , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/diagnóstico , Estudos Prospectivos , Idoso , Reino Unido/epidemiologia , Adulto , Fatores Etários , Incidência , Fatores de Risco , Modelos de Riscos Proporcionais , Pontuação de Propensão
5.
Bioact Mater ; 41: 193-206, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39149597

RESUMO

Regulating macrophage phenotypes to reconcile the conflict between bacterial suppression and tissue regeneration is ideal for treating infectious skin wounds. Here, an injectable immunoregulatory hydrogel (SrmE20) that sequentially drives macrophage phenotypic polarization (M0 to M1, then to M2) was constructed by integrating anti-inflammatory components and proinflammatory solvents. In vitro experiments demonstrated that the proinflammatory solvent ethanol stabilized the hydrogel structure, maintained the phenolic hydroxyl group activity, and achieved macrophages' proinflammatory transition (M0 to M1) to enhance antibacterial effects. With ethanol depletion, the hydrogel's cations and phenolic hydroxyl groups synergistically regulated macrophages' anti-inflammatory transition (M1 to M2) to initiate regeneration. In the anti-contraction full-thickness wound model with infection, this hydrogel effectively eliminated bacteria and even achieved anti-inflammatory M2 macrophage accumulation at three days post-surgery, accelerated angiogenesis and collagen deposition. By sequentially driving macrophage phenotypic polarization, this injectable immunoregulatory hydrogel will bring new guidance for the care and treatment of infected wounds.

6.
Kaohsiung J Med Sci ; 40(9): 837-851, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39023189

RESUMO

The human gut microbiota significantly impacts health, including liver conditions like liver cirrhosis (LC) and spontaneous bacterial peritonitis (SBP). Immunoglobulin A (IgA) plays a central role in maintaining gut microbial balance. Understanding IgA's interplay with gut microbiota and liver health is crucial. This study explores the relationship between fecal IgA levels, gut microbiota, and liver injury severity. A total of 69 LC patients and 30 healthy controls were studied. Fecal IgA levels were measured using ELISA, and IgA-coated bacteria were quantified via flow cytometry. Microbiota diversity and composition were assessed through 16S rRNA sequencing. Liver injury severity was graded using the Child-Pugh score. Statistical analyses determined correlations. LC patients had higher fecal IgA levels than controls, correlating positively with liver injury severity. Microbiota diversity decreased with severity, accompanied by shifts in composition favoring pro-inflammatory species. Ralstonia abundance positively correlated with liver injury, whereas Faecalibacterium showed a negative correlation. Specific microbial markers for SBP were identified. Functional profiling revealed altered microbial functionalities in LC and SBP. Elevated fecal IgA levels, coupled with microbiota alterations, correlate with liver injury severity in LC patients. Modulating gut microbiota could be a promising strategy for managing liver-related conditions. Further research is needed to understand underlying mechanisms and translate findings into clinical practice, potentially improving patient outcomes.


Assuntos
Fezes , Microbioma Gastrointestinal , Imunoglobulina A , Cirrose Hepática , Peritonite , RNA Ribossômico 16S , Humanos , Cirrose Hepática/microbiologia , Peritonite/microbiologia , Peritonite/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Fezes/microbiologia , RNA Ribossômico 16S/genética , Idoso , Adulto , Estudos de Casos e Controles
7.
Nat Commun ; 15(1): 6211, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39043643

RESUMO

The functions of natural killer (NK) and T cells in innate and adaptive immunity, as well as their functions in tumor eradication, are complementary and intertwined. Here we show that utilization of multi-specific antibodies or nano-antibodies capable of simultaneously targeting both NK and T cells could be a valuable approach in cancer immunotherapy. Here, we introduce a tri-specific Nano-Antibody (Tri-NAb), generated by immobilizing three types of monoclonal antibodies (mAbs), using an optimized albumin/polyester composite nanoparticle conjugated with anti-Fc antibody. This Tri-NAb, targeting PDL1, 4-1BB, and NKG2A (or TIGIT) simultaneously, effectively binds to NK and CD8+ T cells, triggering their activation and proliferation, while facilitating their interaction with tumor cells, thereby inducing efficient tumor killing. Importantly, the antitumor efficacy of Tri-NAb is validated in multiple models, including patient-derived tumor organoids and humanized mice, highlighting the translational potential of NK and T cell co-targeting.


Assuntos
Anticorpos Monoclonais , Linfócitos T CD8-Positivos , Células Matadoras Naturais , Nanopartículas , Células Matadoras Naturais/imunologia , Animais , Humanos , Camundongos , Nanopartículas/química , Anticorpos Monoclonais/imunologia , Linhagem Celular Tumoral , Linfócitos T CD8-Positivos/imunologia , Imunoterapia/métodos , Neoplasias/imunologia , Neoplasias/terapia , Antígeno B7-H1/imunologia , Subfamília C de Receptores Semelhantes a Lectina de Células NK/imunologia , Feminino , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Camundongos Endogâmicos NOD
8.
Artigo em Inglês | MEDLINE | ID: mdl-39031457

RESUMO

BACKGROUND AND AIMS: Whether the natural course of ulcerative colitis (UC) in mainland China is similar or different from that in Western countries is unknown, and data on it is limited. We aimed to provide a comprehensive description of the natural course of UC in China and compare it with Western UC patients. METHODS: Based on a prospective Chinese nationwide registry of consecutive patients with inflammatory bowel diseases, the medical treatments and natural history of UC were described in detail, including disease extension, surgery, and neoplasia. The Cox regression model was used to identify factors associated with poor outcomes. RESULTS: A total of 1081 UC patients were included with a median follow-up duration of 5.3 years. The overall cumulative exposure was 99.1% to 5-aminosalicylic acids, 52.1% to corticosteroids, 25.6% to immunomodulators, and 15.4% to biologics. Disease extent at diagnosis was proctitis in 26.9%, left-sided colitis in 34.8%, and extensive colitis in 38.3%. Of 667 patients with proctitis and left-sided colitis, 380 (57.0%) experienced disease extent progression. A total of 58 (5.4%) UC patients underwent colectomy, demonstrating cumulative proportions of surgery at 1, 5, and 10 years after diagnosis of 0.6%, 3.4%, and 8.2%, respectively. In addition, 23 (2.1%) UC patients were diagnosed with neoplasia, demonstrating cumulative proportions of neoplasia at 1, 5, and 10 years after diagnosis of 0.5%, 1.0%, and 3.5%, respectively. CONCLUSIONS: Chinese UC patients had similar cumulative proportions of exposure to IBD-specific treatments but a lower surgical rate than patients in Western countries, indicating a different natural course, and close monitoring needs for UC in China. However, these results must be confirmed in population-based studies because the hospital-based cohort in our study might lead to selection bias.

9.
BMC Musculoskelet Disord ; 25(1): 526, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982393

RESUMO

BACKGROUND AND OBJECTIVE: Complex acetabular fractures involving quadrilateral areas are more challenging to treat during surgery. To date, there has been no ideal internal fixation for these acetabular fractures. The purpose of this study was to evaluate the biomechanical stability of complex acetabular fractures using a dynamic anterior titanium-plate screw system of the quadrilateral area (DAPSQ) by simulating the standing and sitting positions of pelvic specimens. MATERIALS AND METHODS: Eight formal in-preserved cadaveric pelvises aged 30-50 years were selected as the research objects. First, one hip of the normal pelvises was randomly used as the control model (group B) for measurement, and then one hip of the pelvises was randomly selected to make the fracture model in the 8 intact pelvises as the experimental model (group A) for measurement. In group A, acetabular both-column fractures in the quadrilateral area were established, and the fractures were fixed by DAPSQ. The biomechanical testing machine was used to load (simulated physiological load) from 400 N to 700 N at a 1 mm/min speed for 30 s in the vertical direction when the specimens were measured at random in simulated standing or sitting positions in groups. The horizontal displacement and longitudinal displacement of the acetabular fractures in the quadrilateral area were measured in both the standing and sitting simulations. RESULTS: As the load increased, no dislocation or internal fixation breakage occurred during the measurements. In the standing position, the horizontal displacement of the quadrilateral area fractures in group A and group B appeared to be less than 1 mm with loads ranging from 400 N to 700 N, and there was no significant difference between group A and group B (p > 0.05). The longitudinal displacement appeared to be greater than 1 mm with a load of 700 mm in group A (700 N, 2 cases), and the difference was significant between group A and group B (p < 0.05). In the sitting position, the horizontal and longitudinal displacements of the quadrilateral areas were within 0.5 mm in group A and group B, and there was no significant difference between group A and group B (p > 0.05). CONCLUSION: For complex acetabular fractures in the quadrilateral area, DAPSQ fixation may provide early sitting stability, but it is inappropriate for patients to stand too early.


Assuntos
Acetábulo , Placas Ósseas , Parafusos Ósseos , Fixação Interna de Fraturas , Fraturas Ósseas , Titânio , Humanos , Acetábulo/cirurgia , Acetábulo/lesões , Fenômenos Biomecânicos , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/métodos , Adulto , Pessoa de Meia-Idade , Fraturas Ósseas/cirurgia , Fraturas Ósseas/fisiopatologia , Masculino , Feminino , Cadáver
10.
J Craniomaxillofac Surg ; 52(9): 1024-1029, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39025694

RESUMO

Salivary collection (SC) following surgery for oral cancer represents an underreported and unrecognized complication. Our study aimed to evaluate the efficacy of parotideomasseteric fascia flap (PFF) in preventing postoperative SC, comparing its effectiveness with other conventional methods. Between November 2019 and January 2023, 221 patients diagnosed with oral squamous cell carcinoma (OSCC) undergoing wide tumor ablation and neck dissection at Xiangya Hospital were included in the study. Patients were randomly allocated into four groups based on different intraoperative techniques to assess the preventive efficacy of PFF against SC. The incidence of SC in the PFF group was only 5.9%, which was significantly lower than the other three groups (p < 0.05). Among the 221 patients, the highest SC incidence occurred in buccal cancer cases (19.6%). However, in the PFF group, the incidence was not significantly different (9.5%; p > 0.05). Univariate analysis revealed a higher SC incidence associated with advanced clinical T stage (p = 0.02), N(+) stage (p = 0.01), low average serum albumin (SA) level (p = 0.00), and a large parotid wound (p = 0.00). In multivariate analysis, only average SA (p = 0.01; odds ratio [OR] 4.104; 95% CI 0.921-11.746) emerged as the most prevalent factor predisposing to SC. The utilization of PFF demonstrated a notable reduction in the incidence of postoperative SC, establishing it as a safe, effective, and convenient method for patients undergoing radical ablation for OSCC.


Assuntos
Fáscia , Neoplasias Bucais , Complicações Pós-Operatórias , Retalhos Cirúrgicos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Bucais/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Fáscia/transplante , Idoso , Glândula Parótida/cirurgia , Adulto , Esvaziamento Cervical/métodos , Incidência , Saliva
11.
Nanoscale ; 16(24): 11762-11773, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38869001

RESUMO

Nanohydroxyapatite (nHAp) has attracted significant attention for its tumor suppression and tumor microenvironment modulation capabilities. However, a strong tendency to aggregate greatly affects its anti-tumor efficiency. To address this issue, a hydrogel platform consisting of thiolated hyaluronic acid (HA-SH) modified nanohydroxyapatite (nHAp-HA) and HA-SH was developed for sustained delivery of nHAp for melanoma therapy. The hydrophilic and negatively charged HA-SH significantly improved the size dispersion and stability of nHAp in aqueous media while conferring nHAp targeting effects. Covalent sulfhydryl self-cross-linking between HA-SH and nHAp-HA groups ensured homogeneous dispersion of nHAp in the matrix material. Meanwhile, the modification of HA-SH conferred the targeting properties of nHAp and enhanced cellular uptake through the HA/CD44 receptor. The hydrogel platform could effectively reduce the aggregation of nHAp and release nHAp in a sustained and orderly manner. Antitumor experiments showed that the modified nHAp-HA retained the tumor cytotoxicity of nHAp in vitro and inhibited the growth of highly malignant melanomas up to 78.6% while being able to induce the differentiation of macrophages to the M1 pro-inflammatory and antitumor phenotype. This study will broaden the application of nanohydroxyapatite in tumor therapy.


Assuntos
Durapatita , Ácido Hialurônico , Hidrogéis , Melanoma , Durapatita/química , Durapatita/farmacologia , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Camundongos , Melanoma/tratamento farmacológico , Melanoma/patologia , Melanoma/metabolismo , Linhagem Celular Tumoral , Humanos , Receptores de Hialuronatos/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Nanopartículas/química , Células RAW 264.7
12.
iScience ; 27(6): 109979, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38832007

RESUMO

This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized by the Warburg effect, and the dynamic interplay between cancer cells and mitochondria. The role of cancer stem cells (CSCs) in treatment resistance and the regulatory influence of non-coding RNAs, such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are studied. The chapter emphasizes future directions, encompassing advancements in immunotherapy, strategies to counter adaptive resistance, integration of artificial intelligence for predictive modeling, and the identification of biomarkers for personalized treatment. The comprehensive exploration of these hallmarks provides a foundation for innovative therapeutic approaches, aiming to navigate the complex landscape of cancer resistance and enhance patient outcomes.

13.
BMC Surg ; 24(1): 194, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38907190

RESUMO

BACKGROUND: posterior pedicle screw fixation is common method, one of the most severe complications is iatrogenic vascular damage, no report investigated association of different introversion angles (INTAs) and length of pedicle screw. The aims were to investigate the optimal introversion angle and length of pedicle screw for improving the safety of the operation, and to analyze the differences of vascular damage types at L1-S1. METHODS: Lumbar CT imaging data from110 patients were analyzed by DICOM software, and all parameters were measured by new Cartesian coordinate system, INTAs (L1-L5:5°,10°,15°,S1: 0°, 5°,10°,15°), DO-AVC (the distance between the origin (O) with anterior vertebral cortex (AVC)), DAVC-PGVs (the distance between AVC and the prevertebral great vessels (PGVs)), DO-PGVs (the distance between the O and PGVs). At different INTAs, DAVC-PGVs were divided into four grades: Grade III: DAVC-PGVs ≤ 3 mm, Grade II: 3 mm < DAVC-PGVs ≤ 5 mm, Grade I: DAVC-PGVs > 5 mm, and N: the not touching PGVs. RESULTS: The optimal INTA was 5° at L1-L3, the left was 5° and the right was 15° at L4, and screw length was less than 50 mm at L1-L4. At L5, the left optimal INTA was 5° and the right was 10°, and screw length was less than 45 mm. The optimal INTA was 15° at S1, and screw length was less than 50 mm. However, screw length was less than 40 mm when the INTA was 0° or 5° at S1. CONCLUSIONS: At L5-S1, the risk of vascular injury is the highest. INTA and length of the pedicle screw in lumbar operation are closely related. 3 mm interval of screw length may be more preferable to reduce vascular damage.


Assuntos
Vértebras Lombares , Parafusos Pediculares , Fusão Vertebral , Lesões do Sistema Vascular , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Vértebras Lombares/cirurgia , Vértebras Lombares/diagnóstico por imagem , Idoso , Lesões do Sistema Vascular/prevenção & controle , Lesões do Sistema Vascular/etiologia , Adulto , Fusão Vertebral/métodos , Fusão Vertebral/instrumentação , Tomografia Computadorizada por Raios X , Sacro/cirurgia , Sacro/diagnóstico por imagem , Sacro/lesões , Estudos Retrospectivos
14.
Aging Dis ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38913050

RESUMO

This comprehensive review navigates the complex relationship between cellular aging, senescence, and cancer, unraveling the determinants of cellular fate. Beginning with an overview of cellular aging's significance in cancer, the review explores processes, changes, and molecular pathways influencing senescence. The review explores senescence as a dual mechanism in cancer, acting as a suppressor and contributor, focusing on its impact on therapy response. This review highlights opportunities for cancer therapies that target cellular senescence. The review further examines the senescence-associated secretory phenotype and strategies to modulate cellular aging to influence tumor behavior. Additionally, the review highlights the mechanisms of senescence escape in aging and cancer cells, emphasizing their impact on cancer prognosis and resistance to therapy. The article addresses current advances, unexplored aspects, and future perspectives in understanding cellular aging and senescence in cancer.

15.
Chem Commun (Camb) ; 60(55): 7069-7072, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38899972

RESUMO

Ru-doped Co9S8 hollow porous polyhedrons (Ru-Co9S8 HPPs) derived from zeolitic-imidazolate-frameworks were synthesized through hydrothermal coprecipitation and thermal decomposition methods. The results indicate that Ru-Co9S8-500 HPPs possess a strong Ru-Co synergistic effect, large electrochemical surface area, and sufficient active sites, endowing them with excellent hydrogen evolution reaction performance.

16.
Cell Prolif ; : e13697, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38943472

RESUMO

Distant metastasis remains the primary cause of morbidity in patients with breast cancer. Hence, the development of more efficacious strategies and the exploration of potential targets for patients with metastatic breast cancer are urgently needed. The data of six patients with breast cancer brain metastases (BCBrM) from two centres were collected, and a comprehensive landscape of the entire tumour ecosystem was generated through the utilisation of single-cell RNA sequencing. We utilised the Monocle2 and CellChat algorithms to investigate the interrelationships among each subcluster. In addition, multiple signatures were collected to evaluate key components of the subclusters through multi-omics methodologies. Finally, we elucidated common expression programs of malignant cells, and experiments were conducted in vitro and in vivo to determine the functions of interleukin enhancer-binding factor 2 (ILF2), which is a key gene in the metastasis module, in BCBrM progression. We found that subclusters in each major cell type exhibited diverse characteristics. Besides, our study indicated that ILF2 was specifically associated with BCBrM, and experimental validations further demonstrated that ILF2 deficiency hindered BCBrM progression. Our study offers novel perspectives on the heterogeneity of BCBrM and suggests that ILF2 could serve as a promising biomarker or therapeutic target for BCBrM.

17.
Bioresour Technol ; 406: 131008, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38897547

RESUMO

This study investigated the nutrient removal and microbial community succession in moving bed biofilm reactor under stable and three levels of influent carbon/nitrogen (C/N) ratio fluctuation (± 10%, ± 20%, and ± 30%). Under the conditions of influent C/N ratio fluctuation, the removal efficiency of COD and PO43--P decreased 4.7-6.4% and 3.7-12.9%, respectively, while the nitrogen removal was almost unaffected. A sharp decrease in the content of culturable functional bacteria related to nitrogen and phosphorus removal including nitrite-oxidizing bacteria (NOB), aerobic denitrifying bacteria (DNB), and polyphosphate-accumulating organisms (PAOs) from the carrier biofilm was observed. Sequencing analysis revealed that the abundance of Candidatus Competibacter increased 10.3-25.9% and became the dominant genus responsible for denitrification, potentially indicating that nitrate was removed via endogenous denitrification under the influent C/N ratio fluctuation. The above results will provide basic data for the nutrient removal in decentralized wastewater treatment under highly variable influent conditions.


Assuntos
Bactérias , Biofilmes , Reatores Biológicos , Carbono , Nitrogênio , Nitrogênio/metabolismo , Reatores Biológicos/microbiologia , Carbono/metabolismo , Bactérias/metabolismo , Bactérias/genética , Desnitrificação , Fósforo , Purificação da Água/métodos , Nutrientes/metabolismo , Análise da Demanda Biológica de Oxigênio , Águas Residuárias/microbiologia
18.
Int Immunopharmacol ; 138: 112452, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-38943972

RESUMO

Peripheral nerve injury seriously endangers human life and health, but there is no clinical drug for the treatment of peripheral nerve injury, so it is imperative to develop drugs to promote the repair of peripheral nerve injury. Erythropoietin (EPO) not only has the traditional role of promoting erythropoiesis, but also has a tissue-protective effect. Over the past few decades, researchers have confirmed that EPO has neuroprotective effects. However, side effects caused by long-term use of EPO limited its clinical application. Therefore, EPO derivatives with low side effects have been explored. Among them, ARA290 has shown significant protective effects on the nervous system, but the biggest disadvantage of ARA290, its short half-life, limits its application. To address the short half-life issue, the researchers modified ARA290 with thioether cyclization to generate a thioether cyclized helical B peptide (CHBP). ARA290 and CHBP have promising applications as peptide drugs. The neuroprotective effects they exhibit have attracted continuous exploration of their mechanisms of action. This article will review the research on the role of EPO, ARA290 and CHBP in the nervous system around this developmental process, and provide a certain reference for the subsequent research.


Assuntos
Eritropoetina , Fármacos Neuroprotetores , Traumatismos dos Nervos Periféricos , Eritropoetina/uso terapêutico , Humanos , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Animais , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Peptídeos/uso terapêutico , Peptídeos/farmacologia , Oligopeptídeos
19.
J Mater Chem B ; 12(28): 6856-6873, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38904349

RESUMO

The management of chronic infected wounds poses significant challenges due to frequent bacterial infections, high concentrations of reactive oxygen species, abnormal immune regulation, and impaired angiogenesis. This study introduces a novel, microenvironment-responsive, dual dynamic, and covalently bonded hydrogel, termed OHA-P-TA/G/Mg2+. It is derived from the reaction of tannic acid (TA) with phenylboronic acids (PBA), which are grafted onto oxidized hyaluronic acid (OHA-P-TA), combined with GelMA (G) via a Schiff base and chemical bonds, along with the incorporation of Mg2+. This hydrogel exhibits pH and ROS dual-responsiveness, demonstrating effective antibacterial capacity, antioxidant ability, and the anti-inflammatory ability under distinct acidic and oxidative microenvironments. Furthermore, the release of Mg2+ from the TA-Mg2+ network (TA@Mg2+) promotes the transformation of pro-inflammatory M1 phenotype macrophages to anti-inflammatory M2 phenotype, showing a microenvironment-responsive response. Finally, in vivo results indicate that the OHA-P-TA/G/Mg2+ hydrogel enhances epithelial regeneration, collagen deposition, and neovascularization, showing great potential as an effective dressing for infected wound repair.


Assuntos
Hidrogéis , Magnésio , Taninos , Cicatrização , Taninos/química , Taninos/farmacologia , Cicatrização/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Magnésio/química , Magnésio/farmacologia , Animais , Camundongos , Antibacterianos/química , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Células RAW 264.7 , Staphylococcus aureus/efeitos dos fármacos , Reagentes de Ligações Cruzadas/química , Polifenóis
20.
Medicine (Baltimore) ; 103(20): e38214, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758842

RESUMO

Mendelian randomization (MR) analysis was used to determine the causal relationship between Type 2 diabetes (T2D) and osteomyelitis (OM). We performed MR analysis using pooled data from different large-scale genome-wide association studies (GWAS). Instrumental variables were selected based on genome-wide significance, instrumental strength was assessed using F-values, and thresholds for the number of exposed phenotypes were further adjusted by Bonferroni correction. univariable and multivariable MR analyses were performed to assess causal effects and proportions mediated by T2D. IVW (inverse variance weighting) showed a significant genetic effect of osteomyelitis on the following: After correction by Bonferroni, univariable analyses showed that childhood body mass index (BMI) was not significantly associated with genetic susceptibility to OM [odds ratio (OR), 1.26; 95% confidence interval (CI), 1.02, 1.55; P = .030], not significantly associated with adulthood BMI (OR, 1.28; 95% CI, 1.02, 1.61; P = .034), significantly associated with waist circumference (OR, 1.84; 95% CI, 1.51, 2.24; P < .001), and significantly associated with hip circumference (OR, 1.52; 95% CI, 1.31, 1.76; P < .001). Meanwhile, multivariable analyses showed no significant effect of childhood BMI on OM (OR, 1.16; 95% CI, 0.84, 1.62; P = .370), no significant effect of adulthood BMI on OM (OR, 0.42; 95% CI, 0.21, 0.84; P = .015), a significant association between waist circumference and OM (OR, 4.30; 95% CI, 1.89, 9.82; P = .001), T2D mediated 10% (95% CI, 0.02, 0.14), and no significant association between hip circumference and OM (OR, 1.01; 95% CI, 0.54, 1.90; P = .968). Our study provides evidence for a genetically predicted causal relationship among obesity, T2D, and OM. We demonstrate that increased waist circumference is positively associated with an increased risk of OM and that T2D mediates this relationship. Clinicians should be more cautious in the perioperative management of osteomyelitis surgery in obese patients with T2D. In addition, waist circumference may be a more important criterion to emphasize and strictly control than other measures of obesity.


Assuntos
Índice de Massa Corporal , Diabetes Mellitus Tipo 2 , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Obesidade , Osteomielite , Humanos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Osteomielite/genética , Osteomielite/epidemiologia , Obesidade/genética , Obesidade/complicações , Predisposição Genética para Doença , Circunferência da Cintura , Polimorfismo de Nucleotídeo Único , Masculino
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