Search

CO2 is highly stable and therefore extremely difficult to be reduced at room temperature even by photocatalysis. Herein, a series of g-C3N4/Bi2WO6 composites have been synthesized through a facile in situ hydrothermal approach, which demonstrated greatly enhanced response to visible light, and consequently a remarkably enhanced CO2 selective photoreduction to CO. The g-C3N4 content and synthesis parameters of these composites have been tuned to obtain the optimized photocatalytic activity with a peak CO production rate of 5.19 μmol g−1 h−1 under visible light irradiation at room temperature, which was 22 and 6.4 times that on pure g-C3N4 and Bi2WO6, respectively. Based on the matched band energy potentials between g-C3N4 and Bi2WO6 in the synthesized composites, a possible Z-scheme mechanism, which features a significantly promoted separation of photo-generated carriers under visible light irradiation by the composites, has been proposed to account for the distinctive CO2 photoreduction performance. [ABSTRACT FROM AUTHOR]

It is highly desired to exploit non-noble metal oxide catalysts for superseding the Pt-based material and achieving long-term oxygen reduction reaction (ORR). Herein, a FeO-based ORR catalyst is firstly designed and synthesized by a one-pot pyrolysis strategy using FeCl 3 and N-doped carbon nanosheets (NCNSs) as precursors. The NCNSs substrate play the important role to control the size of gained FeO at nanodot level (near 2.5 nm). The supersmall FeO nanodots, uniformly dispersion on the NCNSs, which enhance the touching areas with the NCNSs substrate and expose richen active sites. The introduction of FeO nanodots improve the graphitization degree of the composite and form Fe-N bonds in FeO/NCNSs, then exhibiting excellent electrocatalytic performance and long-term stability. The catalyst displays a high half-wave potential and small Tafel slope of 0.94 V and 56.9 mV dec−1 in the 4 electron ORR process, respectively. Meanwhile, it demonstrates superior tolerance to methanol. Noting, after 150 h i t-test, the current density only drops by 10.7%, even better than the durability performance of many catalysts after 10 h. The theoretical calculations further reveal that the OH* adsorption on the surface of FeO/NCNSs in real reaction environment is beneficial for embedding the FeO NDs in N 6 hollow of NCNSs, which sustains the highly efficient ORR activity under the long-term running conditions. Our work opens a new era for the novel FeO-based ORR catalysts and provides a design reference for the long-term ORR electrode. [Display omitted] [ABSTRACT FROM AUTHOR]

Key Clinical Message: This article reports a case of mediastinal lymph node tuberculosis with no obvious symptoms and a concealed focus. This patient, a 33‐year‐old male, suffered from pain behind the sternum after eating. He underwent three gastroscopic examinations and two fine needle punctures guided by ultrasound gastroscopy but was not diagnosed. Chest‐enhanced CT revealed a mediastinal mass compressing the adjacent esophagus, suggesting the possibility of enlarged lymph nodes. Furthermore, T cells from patients infected with tuberculosis tested positive. Ultrasound bronchoscopy revealed enlarged lymph nodes in area 7, and then EBUS‐TBNA was performed in that region. Only a few scattered lymphocytes and necrotic tissue were found under the biopsy microscope. The EBUS‐TBNA biopsy Xpert MTB/RIF showed low positive results, and the EBUS‐TBNA puncture fluid Xpert MTB/RIF was positive. Therefore, he was diagnosed with mediastinal lymph node tuberculosis. After antituberculosis treatment with the 2HREZ/10HRE regimen, the patient's pain behind the sternum gradually alleviated, and the enlarged mediastinal lymph nodes gradually narrowed. [ABSTRACT FROM AUTHOR]

The tumor develops defense tactics, including conversing the mechanical characteristics of tumor cells and their surrounding environment. A recent study reported that cholesterol depletion stiffens tumor cells, which could enhance adaptive T-cell immunotherapy. However, it remains unclear whether reducing the cholesterol in tumor cells contributes to re-educating the stiff tumor matrix, which serves as a physical barrier against drug penetration. Herein, we found that depleting cholesterol from tumor cells can demolish the intratumor physical barrier by disrupting the mechanical signal transduction between tumor cells and the extracellular matrix through the destruction of lipid rafts. This disruption allows nanoparticles (H/S@hNP) to penetrate deeply, resulting in improved photodynamic treatment. Our research also indicates that cholesterol depletion can inhibit the epithelial-mesenchymal transition and repolarize tumor-associated macrophages from M2 to M1, demonstrating the essential role of cholesterol in tumor progression. Overall, this study reveals that a cholesterol-depleted, softened tumor matrix reduces the difficulty of drug penetration, leading to enhanced antitumor therapeutics. [Display omitted] • H/S@hNP could soften the stiff tumor matrix via cholesterol-depletion strategy. • H/S@hNP mediated cholesterol depletion enhanced nanoparticle penetration and photodynamic therapy antitumor efficacy. • H/S@hNP could hamper epithelial-mesenchymal transition and switch tumor-associated macrophages from M2 to M1. [ABSTRACT FROM AUTHOR]

In contrast to the decreasing trends in developed countries, the incidence and mortality rates of cervical squamous cell carcinoma in China have increased significantly. The screening and identification of reliable biomarkers and candidate drug targets for cervical squamous cell carcinoma are urgently needed to improve the survival rate and quality of life of patients. In this study, we demonstrated that the expression of MUC1 was greater in neoplastic tissues than in non-neoplastic tissues of the cervix, and cervical squamous cell carcinoma patients with high MUC1 expression had significantly worse overall survival than did those with low MUC1 expression, indicating its potential for early diagnosis of cervical squamous cell carcinoma. Next, we explored the regulatory mechanism of MUC1 in cervical squamous cell carcinoma. MUC1 could upregulate ITGA2 and ITGA3 expression via ERK phosphorylation, promoting the proliferation and metastasis of cervical cancer cells. Further knockdown of ITGA2 and ITGA3 significantly inhibited the tumorigenesis of cervical cancer cells. Moreover, we designed a combination drug regimen comprising MUC1-siRNA and a novel ERK inhibitor in vivo and found that the combination of these drugs achieved better results in animals with xenografts than did MUC1 alone. Overall, we discovered a novel regulatory pathway, MUC1/ERK/ITGA2/3, in cervical squamous cell carcinoma that may serve as a potential biomarker and therapeutic target in the future. Summary: MUC1 is overexpressed in cervical squamous cell carcinoma. MUC1 regulates ERK phosphorylation, and subsequently upregulates ITGA2 and ITGA3 expression to promote tumorigenesis in cervical squamous cell carcinoma. A combination drug regimen targeting MUC1 and ERK achieved better results compared than MUC1 alone. [ABSTRACT FROM AUTHOR]

Near infrared light, especially the second near‐infrared light (NIR II) biowindows with deep penetration and high sensitivity are widely used for optical diagnosis and phototherapy. Here, a novel kind of 2D SnTe@MnO2‐SP nanosheet (NS)‐based nanoplatform is developed for cancer theranostics with NIR II‐mediated precise optical imaging and effective photothermal ablation of mouse xenografted tumors. The 2D SnTe@MnO2‐SP NSs are fabricated via a facile method combining ball‐milling and liquid exfoliation for synthesis of SnTe NSs, and surface coating MnO2 shell and soybean phospholipid (SP). The ultrathin SnTe@MnO2‐SP NSs reveal notably high photothermal conversion efficiency (38.2% in NIR I and 43.9% in NIR II). The SnTe@MnO2‐SP NSs inherently feature tumor microenvironment (TME)‐responsive biodegradability, and the main metabolite TeO32− shows great antitumor effect, coupling synergetic chemotherapy for cancer. Moreover, the SnTe@MnO2‐SP NSs also exhibit great potential for fluorescence, photoacoustic (PA), and photothermal imaging agents in the NIR II biowindow with much higher resolution and sensitivity. This is the first report, as far as is known, with such an inorganic nanoagent setting fluorescence/PA/photothermal imaging and photothermal therapy in NIR II biowindow and TME‐responsive biodegradability rolled into one, which provide insight into the clinical potential for cancer theranostics. [ABSTRACT FROM AUTHOR]

Background: sCD25 is an important immune molecule for T cell regulation. Tracking the detection of plasma sCD25 plays an important role in the evaluation of immune function, progression, and prognosis of tuberculosis (TB) patients. This study analyzed the association of plasma sCD25 levels with clinical, laboratory, CT imaging characteristics, and clinical outcome of TB patients. Methods: The clinical data of 303 TB patients treated in the Fifth People's Hospital of Suzhou from October 2019 to January 2022 were retrospectively analyzed. The levels of sCD25 in plasma were detected by ELISA. According to the cut-off threshold of plasma sCD25 levels, the patients were divided into a low-value group (Group TB1) and a high-value group (Group TB2). The association of plasma sCD25 levels with clinical, laboratory, and CT imaging characteristics of TB patients, as well as their TB treatment outcome were analyzed. Results: The levels of plasma sCD25 of patients with TB patients were higher than that of the healthy control group (P < 0.01). Among the 303 TB patients, the levels were increased in Group TB2 patients (0.602 ± 0.216 vs. 1.717 ± 0.604 ng/ml, P < 0.001), and there was a progressive reduction after anti-TB treatment. Furthermore, patients in Group TB2 showed higher positive rates in sputum smear (52.0% vs. 34.3%; P = 0.003), sputum culture (69.7% vs. 56.9%; P = 0.032), Xpert MTB/RIF (66.3% vs. 51.2%; P = 0.013) and TB-DNA (51.5% vs. 31.2%; P = 0.001) than those in Group TB1. Patients in Group TB2 had higher incidence in cough (78.8% vs. 62.3%; P = 0.004), expectoration (64.4% vs. 45.1%; P = 0.001), concomitant extrapulmonary TB (14.1% vs. 5.9%; P = 0.016), cavities (47.9% vs. 34.0%; P = 0.022), and unfavorable outcomes after anti-TB treatment. Conclusion: The clinical, laboratory and radiological manifestations of TB patients with high plasma sCD25 levels indicate that the disease is more severe. Tracking plasma sCD25 detection of TB patients has evident clinical significance. It is noteworthy that when the plasma sCD25 levels are significantly elevated, patients should be cautious of the TB progression and disease severity. [ABSTRACT FROM AUTHOR]

Exploring the influence of pyrazinamide exposure and susceptibility on treatment response is crucial for optimizing the management of multidrug-resistant tuberculosis (MDR-TB). This study aimed to investigate the association between pyrazinamide exposure, susceptibility, and response to MDR-TB treatment, as well as find clinical thresholds for pyrazinamide. A prospective multi-center cohort study of participants with MDR-TB using pyrazinamide was conducted in three TB-designated hospitals in China. Univariate and multivariate analyses were applied to investigate the associations. Classification and Regression Tree (CART) analysis was used to identify clinical thresholds, which were further evaluated by multivariate analysis and receiver operating characteristic (ROC) curves. The study included 143 patients with MDR-TB. The exposure/susceptibility ratio of pyrazinamide was associated with two-month culture conversion (adjusted risk ratio (aRR), 1.1; 95% confidence interval (CI), 1.07–1.20), six-month culture conversion (aRR, 1.1; 95% CI, 1.06–1.16), treatment success (aRR, 1.07; 95% CI, 1.03–1.10), as well as culture conversion time (adjusted hazard ratio (aHR) 1.18; 95% CI,1.14–1.23). The threshold for optimal improvement in sputum culture results at the sixth month of treatment was determined to be a pyrazinamide AUC0–24h/MIC ratio of 7.8. In conclusion, the exposure/susceptibility ratio of pyrazinamide is associated with the treatment response of MDR-TB, which may change in different Group A drug-based regimens. [ABSTRACT FROM AUTHOR]

Biomimetic delivery systems (BDSs), inspired by the intricate designs of biological systems, have emerged as a groundbreaking paradigm in nanomedicine, offering unparalleled advantages in therapeutic delivery. These systems, encompassing platforms such as liposomes, protein-based nanoparticles, extracellular vesicles, and polysaccharides, are lauded for their targeted delivery, minimized side effects, and enhanced therapeutic outcomes. However, the translation of BDSs from research settings to clinical applications is fraught with challenges, including reproducibility concerns, physiological stability, and rigorous efficacy and safety evaluations. Furthermore, the innovative nature of BDSs demands the reevaluation and evolution of existing regulatory and ethical frameworks. This review provides an overview of BDSs and delves into the multifaceted translational challenges and present emerging solutions, underscored by real-world case studies. Emphasizing the potential of BDSs to redefine healthcare, we advocate for sustained interdisciplinary collaboration and research. As our understanding of biological systems deepens, the future of BDSs in clinical translation appears promising, with a focus on personalized medicine and refined patient-specific delivery systems. [ABSTRACT FROM AUTHOR]

Abstract After emitted from incomplete combustion of fossil fuels and biomass, ambient black carbon (BC) was then undergone photochemical oxidization processes in the air to form aged BC particles, also called oxidized BC (OBC). This study aimed to investigate the interactions between oxidative stress, autophagy and apoptosis induced by OBC in A549 cells and to explore associated molecular mechanisms. First, OBC could stimulate oxidative stress, autophagy and apoptosis dose-dependently, as evidenced by increased intercellular reactive oxygen species (ROS) levels, up-regulated autophagosome markers (light chain 3, LC3), and elevated apoptosis rate. Inhibitors of oxidative stress (N -acetylcysteine, NAC), autophagy (bafilomycin A1, Baf) and apoptosis (Z -DEVD-FMK) were used to investigate their interactions. NAC pretreatment could significantly reduce autophagy and apoptosis. Additionally, pretreatment with Baf or Z -DEVD-FMK could also significantly suppress the other two biological effects. Furthermore, OBC up regulated the expressions of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), phosphorylated protein kinase B (Akt) and mammalian target of rapamycin (mTOR). The Akt inhibitor (MK-2206) significantly reduced both autophagy and apoptosis. Taken together, dual-direction regulation existed between each two of oxidative stress, autophagy, and apoptosis in A549 cells exposed to OBC. In addition, the autophagy process is modulated by the PI3K/Akt pathway regardless of mTOR activity. Graphical abstract Unlabelled Image Highlights • Oxidized BC containing PAHs activated autophagy, apoptosis and oxidative stress in A549 cells. • Dual-direction regulations existed between autophagy and apoptosis. • Autophagy and apoptosis were regulated by PI3K/Akt pathway. • Autophagy and apoptosis were independent of mTOR pathway [ABSTRACT FROM AUTHOR]

Background: Increasing evidence suggests that FBXW7 has a high frequency of mutations in esophageal squamous cell carcinoma (ESCC). However, the function of FBXW7, especially the mutations, is not clear. This study was designed to investigate the functional significance of FBXW7 loss of function and underlying mechanism in ESCC. Methods: Immunofluorescence was applied to clarify the localization and main isoform of FBXW7 in ESCC cells. Sanger sequencing were performed to explore mutations of FBXW7 in ESCC tissues. Proliferation, colony, invasion and migration assays were performed to examine the functional roles of FBXW7 in ESCC cells in vitro and in vivo. Real-time RT-PCR, immunoblotting, GST-pulldown, LC–MS/MS and co-immunoprecipitation assay were used to explore the molecular mechanism underlying the actions of FBXW7 functional inactivation in ESCC cells. Immunohistochemical staining were used to explore the expression of FBXW7 and MAP4 in ESCC tissues. Results: The main FBXW7 isoform in ESCC cells was the β transcript in the cytoplasm. Functional inactivation of FBXW7 led to activation of the MAPK signaling pathway and upregulation of the downstream MMP3 and VEGFA, which enhanced tumor proliferation cell invasion and migration. Among the five mutation forms screened, S327X (X means truncated mutation) had an effect similar to the FBXW7 deficiency and led to the inactivation of FBXW7 in ESCC cells. Three other point mutations, S382F, D400N and R425C, attenuated but did not eliminate FBXW7 function. The other truncating mutation, S598X, which was located outside of the WD40 domain, revealed a tiny attenuation of FBXW7 in ESCC cells. Notably, MAP4 was identified as a potential target of FBXW7. The threonine T521 of MAP4, which was phosphorylated by CHEK1, played a key role in the FBXW7-related degradation system. Immunohistochemical staining indicated that FBXW7 loss of function was associated with tumor stage and shorter survival of patients with ESCC. Univariate and multivariate Cox proportional hazards regression analyses showed that high FBXW7 and low MAP4 was an independent prognostic indicator and prospective longer survival. Moreover, a combination regimen that included MK-8353 to inhibit the phosphorylation of ERK and bevacizumab to inhibit VEGFA produced potent inhibitory effects on the growth of FBXW7 inactivation xenograft tumors in vivo. Conclusions: This study provided evidence that FBXW7 loss of function promoted ESCC via MAP4 overexpression and ERK phosphorylation, and this novel FBXW7/MAP4/ERK axis may be an efficient target for ESCC treatment. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells exert cytotoxic effects against infected or stressed cells, such as tumor cells, without the limitation of major histocompatibility complex (MHC) I. NK cells secrete perforins to form tunnels to mediate the entry of granzyme into target cells. This strategy, selected by natural evolution, provides a feasible method for the delivery of antitumor drugs against intracellular targets, and avoids drug-resistant mechanisms in tumor cells, such as the pumping out of drugs mediated by multidrug resistance. We constructed pH-labile artificial NK cells (ANKC) based on nature to mediate high levels of drugs in tumor cells to overcome tumor drug resistance. Mesoporous silicon nanoparticles (MSNs) modified with benzaldehyde were designed to function as scaffolds for ANKC. Doxorubicin (Dox), a model antitumor drug, was loaded into the pores of MSNs. Melittin, a pore-forming peptide, was utilized as the gate for mesopores with an acid-labile Schiff base linkage. pH-labile ANKC released melittin and Dox in slightly acidic tumor microenvironments. Melittin, like perforin, assembled tunnels on the plasma membrane or endosome, ensuring the intracellular transportation of Dox. Dox, similar to granzyme, induced the apoptosis of tumor cells. The combinational treatment partially eased the drug resistance mechanism, such as pumping out of drugs, by continuous intracellular drug accumulation mediated by melittin pores. The pH-labile ANKC demonstrated significant Dox enrichment in drug-resistant MCF-7/Adr cells and MCF-7/Adr-based xenograft tumors in a mouse model, which eventually contributed to efficient inhibition of the proliferation and growth of MCF-7/Adr tumors. PH-labile ANKC provided a potential strategy to treat drug-resistant tumors. Schematic graph of constructing ANKC and their antitumor mechanism. [Display omitted] [ABSTRACT FROM AUTHOR]

Ferroptosis, as an effective sensitizer for apoptosis-based cancer treatments, has been elucidated to rely on high levels of intracellular oxidative stress mediated by the accumulation of reactive oxygen species (ROS). However, ferroptosis-related oxidation effect is largely counteracted by the endogenous reductive glutathione (GSH). Here, we constructed a self-assembled metal-organic nanomedicine p53/Ce6@ZF-T, which was composed of p53 plasmid-complexed chlorin e6 (Ce6)-poly(amidoamine), Fe2+-containing mesoporous zeolitic imidazolate framework-8 and naturally derived tannic acid (TA). The highly cytotoxic ROS was continuously produced via Fe2+-mediated and TA-assisted enhanced Fenton reaction as well as Ce6-induced photosensitive reaction, and meanwhile, the intratumoral upregulated p53 expression inactivated glutathione peroxidase 4 (GPX4) to suppress lipid peroxidation (LPO) resistance, thus resulting in amplified oxidative stress and intensified ferroptosis-apoptosis therapy. The notable anticancer efficacy of p53/Ce6@ZF-T both in vitro and in vivo substantially evidenced the high feasibility of oxidative stress-amplified therapeutic modality for enhanced ferroptosis-apoptosis combined therapy, which would be a promising approach in the field of cancer treatment in the future. p53-mediated ferroptosis could remodel the sensitivity of tumors to proapoptotic therapy for intensified ferroptosis-apoptosis combined tumor therapy through an oxidative stress-amplified nanomedicine p53/Ce6@ZF-T. [Display omitted] • An oxidative stress-amplified nanomedicine (p53/Ce6@ZF-T) was designed for inducing ferroptosis-apoptosis antitumor therapy. • p53/Ce6@ZF-T combined Fenton reaction with photodynamic therapy to generate abundant highly cytotoxic ROS. • Tannic acid coating on p53/Ce6@ZF could strengthen Fenton reaction efficacy by accelerating the conversion of Fe3+ to Fe2+. • p53/Ce6@ZF-T showed an excellent expression ability of p53 protein to inactivate GPX4 activity and amplify ferroptosis. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer is the most lethal gynecological cancer which is characterized by extensive peritoneal implantation metastasis and malignant ascites. Despite advances in diagnosis and treatment in recent years, the five-year survival rate is only 25–30%. Therefore, developing multifunctional nanomedicine with abilities of promoting apoptosis and inhibiting migration on tumor cells would be a promising strategy to improve the antitumor effect. Methods and results: In this study, we developed a novel ACaT nanomedicine composed of alendronate, calcium ions and cyclin-dependent kinase 7 (CDK7) inhibitor THZ1. With the average size of 164 nm and zeta potential of 12.4 mV, the spherical ACaT nanoparticles were selectively internalized by tumor cells and effectively accumulated in the tumor site. Results of RNA-sequencing and in vitro experiments showed that ACaT promoted tumor cell apoptosis and inhibited tumor cell migration by arresting the cell cycle, increasing ROS and affecting calcium homeostasis. Weekly intraperitoneally administered of ACaT for 8 cycles significantly inhibited the growth of tumor and prolonged the survival of intraperitoneal xenograft mice. Conclusion: In summary, this study presents a new self-assembly nanomedicine with favorable tumor targeting, antitumor activity and good biocompatibility, providing a novel therapeutic strategy for advanced ovarian cancer. [ABSTRACT FROM AUTHOR]

• A reduced diversity of gut microbiota was observed in tuberculosis (TB) patients. • TB patients had a low abundance of short-chain fatty acid-producing genera. • Active TB patients showed a raised abundance of several conditional pathogens. • Antibiotic use before TB diagnosis could alter the gut microbiota of patients. Background: The aim of this study was to identify the differences in diversity, composition, and function of the gut microbiota between tuberculosis (TB) patients and healthy controls (HCs). Methods: A cross-sectional study was conducted in three cities of China. Stool samples from 94 treatment-naive TB patients and 62 HCs were analyzed by 16S rRNA gene sequencing. TB patients were further divided into antibiotic-free and antibiotic-exposure according to their use of non-specific antibiotics before the TB diagnosis. Results: Compared with HCs, antibiotic-free TB patients presented a different gut microbial community (P < 0.005) and decreased Shannon diversity (P < 0.005). Among TB patients, the relative abundances of short-chain fatty acid (SCFA)-producing genera such as Lachnospiraceae ND3007 group (log2(FC) = −2.74) were lower, while several conditional pathogen-related genera such as Enterococcus (log2(FC) = 12.05) and Rothia (log2(FC) = 6.322) were at higher levels. In addition, 41% of patients received antibiotics before TB diagnosis. Antibiotic exposure was correlated with an additional reduction in α diversity and depletion of SCFA-producing bacteria. Microbial functional analysis revealed that the biosynthesis capacity of amino acids and fatty acids was lower among TB patients compared to HCs. Conclusions: Significant alterations in gut microbiota composition and metabolic pathways of TB patients were observed. Antibiotic exposure could alter the gut microbiota of TB patients, which should be considered in anti-TB treatment. [ABSTRACT FROM AUTHOR]

In clinical practice, PTB patients have concurrent many types of comorbidities such as pneumonia, liver disorder, diabetes mellitus, hematological disorder, and malnutrition. Detecting and treating specific comorbidities and preventing their development are important for PTB patients. However, the prevalence of most comorbid conditions in patients with PTB is not well described. We conducted a large-scale, multicenter, observational study to elucidate and illustrate the prevalence rates of major comorbidities in inpatients at 21 hospitals in China. The 19 specific comorbidities were selected for analysis in this patient cohort, and stratified the inpatient cohort according to age and gender. A total of 355,929 PTB inpatients were included, with a male:female ratio of 1.98 and the proportion of ≥ 65 years PTB inpatients was the most. Approximately 70% of PTB inpatients had at least one defined type of comorbidity. The prevalence of 19 specific comorbidities in inpatients with PTB was analyzed, with pneumonia being the most common comorbidity. The prevalence of most comorbidities was higher in males with PTB except thyroid disorders, mental health disorders, etc. The prevalence of defined most comorbidities in patients with PTB tended to increase with increasing age, although some specific comorbidities tended to increase initially then decrease with increasing age. Our study describes multiple clinically important comorbidities among PTB inpatients, and their prevalence between different gender and age groups. The results will enhance the clinical aptitude of physicians who treat patients with PTB to recognize, diagnose, and treat PTB comorbidities early. [ABSTRACT FROM AUTHOR]

[Display omitted] The characteristics of biofilms have exacerbated the issue of clinical antibiotic resistance, rendering it a pressing challenge in need of resolution. The combination of biofilm-dispersing agents and antibiotics can eliminate biofilms and promote healing synergistically in infected wounds. In this study, we developed a novel nanocomposite hydrogel (NC gel) comprised of the poly(lactic acid)-hyperbranched polyglycerol (PLA-HPG) based bioadhesive nanoparticles (BNPs) and a hydrophilic carboxymethyl chitosan (CS) network. The NC gel was designed to co-deliver two biofilm-dispersing agents (an NO-donor SNO, and an α-amylase Am) and an antibiotic, cefepime (Cef), utilizing a synergistic anti-biofilm mechanism in which Am loosens the matrix structure and NO promotes the release of biofilm bacteria via quorum sensing, and Cef kills bacteria. The drug-loaded NC gel (SNO/BNP/CS@Am-Cef) demonstrated sustained drug release, minimal cytotoxicity, and increased drug-bacterial interactions at the site of infection. When applied to mice infected with methicillin-resistant Staphylococcus aureus (MRSA) biofilms in vivo , SNO/BNP/CS@Am-Cef enhanced biofilm elimination and promoted wound healing compared to traditional antibiotic treatments. Our work demonstrates the feasibility of the co-delivery of biofilm-dispersing agents and antibiotics using the NC gel and presents a promising approach for the polytherapy of bacterial biofilm-related infections. [ABSTRACT FROM AUTHOR]

As the combination of photothermal therapy (PTT) with immunotherapy provides an effective strategy in cancer treatment, a magnetic nanoparticle delivery system was constructed to load indocyanine green (ICG) and immunostimulator R837 hydrochloride (R837) for spatio-temporally PTT/immunotherapy synergism in cancer. This delivery system is composed of Fe 3 O 4 magnetic nanoparticles (MPs) as the core to load ICG and polyethylene glycol polyphenols (DPA-PEG) as the coating layer to load R837, which formed R837 loaded polyphenols coating ICG loaded magnetic nanoparticles (MIRDs). After intravenous injection, the formed MIRDs resulted in long circulation, magnetic resonance imaging (MRI) guides, and magnetic targeting. Once targeting to the tumor, the MIRDs with the near-infrared (NIR) irradiation caused tumor ablation and resulted in tumor-associated antigens releasing to induce the body's immunological response, which was markedly improved it to attack the tumors with the R837 releasing from the outer DPA-PEG. In this case, the synergism of the PTT and immunotherapy inhibited tumor growth, metastasis and recurrence, which resulted in potent anticancer therapeutic effects with few side effect. Unlabelled Image • A magnetic nanoparticle is used as a carrier for magnetic tumor targeting. • Great superparamagnetism of this platform provides a visible treatment by MRI. • Magnetic accumulation of ICG in tumor enhances the PTT effect. • Controlled release of R837 further strengthens the immune response caused by PTT. • This strategy shows great performance in three clinically relevant tumor models. [ABSTRACT FROM AUTHOR]

• MOF nanoshell materials are "star" platforms in biomedicine. • Preparation strategies of MOF nanoshell materials are systematically reviewed. • Drug delivery, biosensing, bioimaging and cancer therapy are involved. • Challenge and future development are prospected. The integration of metal-organic frameworks (MOFs) and nanoshells to construct MOF nanoshell structures offers promising therapeutic platforms for biomedical applications. These MOF nanoshells, which encompass hollow-shells, core-shells, and yolk-shells, exhibit not only the inherent benefits of MOFs, such as large specific surface area, high pore volume, adjustable pore size, rapid cargo transfer and diffusion, excellent biocompatibility, and biodegradability, but also the structural advantages of nanoshells, including a large cavity, high loading capacity, and protective effects. Consequently, MOF nanoshells emerge as ideal materials for biomedical applications. The incorporation of functional nanoparticles or chemotherapeutic molecules with MOF nanoshells enables multi-component synergy due to their adjustable structures, components, and surface modifications, an aspect unattainable by single-component materials. This review article systematically introduces the synthesis strategies for various MOF nanoshells and delves into their applications in biomedicine, including drug delivery, biosensing, bioimaging, and cancer therapy. Finally, the challenges, suggestions, and future prospects of MOF nanoshell structures are discussed. [ABSTRACT FROM AUTHOR]

Lymphocyte-activation gene 3 (LAG-3) plays an important role in regulating T-cell responses and inducing peripheral tolerance. Our aim in this study was to investigate the relationship between LAG-3 and active tuberculosis (ATB) and the impact of LAG-3 blockade on CD8+T cells. Flow cytometry was used to detect the expression of LAG-3 on CD4+T and CD8+T cells in the peripheral blood and bronchoalveolar lavage fluid from ATB patients and to explore the relationship between LAG-3 and ATB. The expression of LAG-3 on CD4+T and CD8+T cells in ATB patients was increased (P < 0.001), and CD8+T cells with high expression of LAG-3 were associated with sputum culture results (P < 0.05). We further analyzed the relationship between the expression of LAG-3 in CD8+T cells and the severity of tuberculosis and found that the expression of LAG-3 on CD8+T cells in smear-positive tuberculosis patients was significantly higher than that in sputum smear-negative tuberculosis patients (P < 0.05). LAG-3 expression on CD8+T cells was negatively correlated with the presence of lung lesions (P < 0.05). After stimulation with a tuberculosis-specific antigen, the expression of LAG-3 on tuberculosis-specific CD8+T cells was also upregulated, and LAG-3-expressing CD8+T cells showed reduced production of IFN-γ, decreased activation, and lower proliferation, while the function of CD8+T cells was restored when LAG-3 signaling was blocked. This study further explored the relationship between immune exhaustion caused by LAG-3 and immune escape of Mycobacterium tuberculosis and revealed that the elevated expression of LAG-3 on CD8+T cells correlates with functional defects of CD8+T cells and the severity of pulmonary TB. • The expression of LAG-3 on CD8 + T cells was elevated in patients with active pulmonary tuberculosis. • The elevate of LAG-3 on CD8 + T cells was associated with severity of Tuberculosis. • Increased LAG-3 results in decreased activation, proliferation, secretion, and killing of CD8 + T cells. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT)-mediated antitumor immune response depends on oxidative stress intensity and subsequent immunogenic cell death (ICD) in tumor cells, yet the inherent antioxidant system restricts reactive oxygen species (ROS)-associated oxidative damage, which is highly correlated with the upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and the downstream products, such as glutathione (GSH). Herein, to overcome this dilemma, we designed a versatile nanoadjuvant (RI@Z-P) to enhance the sensitivity of tumor cells to oxidative stress via Nrf2-specific small interfering RNA (siNrf2). The constructed RI@Z-P could significantly amplify photooxidative stress and achieve robust DNA oxidative damage, activating the stimulator of interferon genes (STING)-dependent immune-sensing to produce interferon-β (IFN-β). Additionally, RI@Z-P together with laser irradiation reinforced tumor immunogenicity by exposing or releasing damage-associated molecular patterns (DAMPs), showing the prominent adjuvant effect for promoting dendritic cell (DC) maturation and T-lymphocyte activation and even alleviating the immunosuppressive microenvironment to some extent. [ABSTRACT FROM AUTHOR]