Ninth Version of the AJCC and UICC Nasopharyngeal Cancer TNM Staging Classification.

Importance: Accurate staging is a fundamental step in treating patients with nasopharyngeal carcinoma (NPC) worldwide; this is crucial not only for prognostication, but also for guiding treatment decisions. The American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor-node-metastasis (TNM) system is the global language for clinicians, researchers, and cancer registries. Continual improvement that aligns with contemporary pattern of care is essential. Objective: To improve the prognostic accuracy and clinical applicability of the eighth edition (TNM-8) for NPC. Design, Setting, and Participants: This multicenter study analyzed patients with NPC with detailed tumor features during January 2014 and December 2015 and was reviewed by experienced radiologists. The data analysis was completed in December 2023. The findings were further confirmed with internal and external validation. Statistical analyses and clinical considerations were reviewed by the AJCC/UICC multidisciplinary head and neck panels and attained consensus. The recommendations were evaluated by the AJCC Evidence-Based Medicine Committee before final endorsement as the ninth version (TNM-9). Main Outcomes and Measures: The primary end point was overall survival. Adjusted hazard ratios of different subgroups were then assessed for confirmation of optimal stage grouping. Results: Of the 4914 patients analyzed, 1264 (25.7%) were female and 3650 (74.3%) were male; the median (SD) age was 48.1 (12.0) years. Advanced radiological extranodal extension (with involvement of adjacent muscles, skin, and/or neurovascular bundles) was identified as an independent adverse factor for all end points: this was added as a criterion for N3. Patients with nonmetastatic disease were regrouped into stages I to III instead of TNM-8 stages I to IVA. Significant hazard discrimination was achieved by grouping T1-2N0-1 as stage I, T3/N2 as stage II, and T4/N3 as stage III. Although the T1-2N0-1 subgroups had comparable 5-year overall survival, subdivisions into IA (T1-T2N0) and IB (T1-T2N1) were recommended due to the distinction in adjusted hazard ratios following adjustment for chemotherapy use. Metastatic disease was exclusively classified as stage IV, and prognostication was further refined by subdivision into IVA (M1a, ≤3 lesions) and IVB (M1b, >3 lesions). TNM-9 demonstrated superiority compared with TNM-8 in major statistical aspects. Conclusion and Relevance: The results of this diagnostic study suggest that the ninth version of TNM staging for NPC, based on robust analyses and a comprehensive review by the AJCC/UICC staging committees, provides an improved staging system for global application and a framework for future incorporation of nonanatomical factors. This will be launched for global application in January 2025.

The Effects of Variation in the GABAA Receptor Gene on Anxious Depression are Mediated by the Functional Connectivity Between the Amygdala and Middle Frontal Gyrus.

Background: γ-aminobutyric acid (GABA) and its main receptor, the GABAA receptor, are implicated in major depressive disorder (MDD). Anxious depression (AD) is deemed to be a primary subtype of MDD. The amygdala and the dorsolateral prefrontal cortex (DLPFC) are key brain regions involved in emotional regulation. These regions contain the most GABAA receptors. Although the GABAergic deficit hypothesis of MDD is generally accepted, few studies have demonstrated how GABAA receptor gene polymorphisms affect the functions of specific brain regions, in particular, the amygdala and the DLPFC. Methods: The sample comprised 83 patients with AD, 70 patients with non-anxious depression (NAD), and 62 healthy controls (HC). All participants underwent genotyping for polymorphisms of GABAA receptor subunit genes, followed by a resting-state fMRI scan. The HAMD-17 was used to evaluate the severity of MDD. ANOVA was performed to obtain the difference in the imaging data, GABAA receptor multi-locus genetic profile scores (MGPS), and HAMD-17 scores among three groups, then the significant differences between AD and NAD groups were identified. Mediating effect analysis was used to explore the role of functional connectivity (FC) between the amygdala and DLPFC in the association between the GABAA receptor gene MGPS and AD clinical features. Results: Compared with the NAD group, the AD group had a higher GABAA receptor MGPS. AD patients exhibited a negative correlation between the MGPS and FC of the right centromedial (CM) subregion, and the right middle frontal gyrus (MFG). A negative correlation was also observed between the MGPS and anxiety/somatic symptoms. More importantly, the right CM and right MFG connectivity mediated the association between the GABAA receptor MGPS and anxiety/somatic symptoms in patients with AD. Conclusion: The decreased FC between the right MFG and right CM subregion mediates the association between GABAA receptor MGPS and AD.

Synergistic Intramolecular Non-Covalent Interactions Enable Robust Pure-Blue TADF Emitters.

Stability-issues of organic light-emitting diodes (OLEDs) employing thermally activated delayed fluorescence (TADF) require further advancements, especially in pure-blue range of CIEy < 0.20, existing a dilemma between color purity and device lifetime. Though improving bond-dissociation-energy (BDE) can effectively improve material intrinsic stability, strategies to simultaneously improve BDE and photophysical performances are still lacking. Herein, it is disclosed that synergistic intramolecular non-covalent interactions (Intra-NI) can achieve not only the highest C─N BDE among blue TADF materials, but enhanced molecular-rigidity, near-unity photoluminescent quantum yields and short delayed lifetime. Pure-blue TADF-OLEDs based on proof-of-concept TADF material realize high external-quantum-efficiency and record-high LT80@500 cd m-2 of 109 h with CIEy = 0.16. Furthermore, deep-blue TADF-sensitized devices exhibit high LT80@500 cd m-2 of 81 h with CIEy = 0.10. The findings provide new insight into the critical role of Intra-NI in OLED materials and open the way to tackling vexing stability issues for developing robust pure-blue organic emitters and other functional materials.

Effects of electroacupuncture combined with paliperidone palmitate long-acting injection on withdrawal symptoms and neurotransmitters in methamphetamine addicts.

OBJECTIVE: To investigate the effects of electroacupuncture combined with paliperidone palmitate long-acting injection (PP-LAI) on withdrawal symptoms and neurotransmitters in methamphetamine (MA) addicts. MATERIALS AND METHODS: A total of 109 methamphetamine addicts, who were treated in the hospital from October 2021 to October 2022, were selected. According to the random number table, the patients were divided into the study group (n=54) and the control group (n=55), in which the control group was treated with PP-LAI and the study group was treated with electroacupuncture on the basis of the control group; the methamphetamine withdrawal symptom score scale was used to assess the therapeutic effect before treatment and within 12 months after treatment; the changes of brain neurotransmitters dopamine, γ-aminobutyric acid, serotonin, acetylcholine values were compared between the two groups. RESULTS: 1) There was no statistical difference in MA withdrawal symptom scores between the two groups before treatment (p>0.05); 2) MA withdrawal symptom scores have a statistically significant difference between the study group and the control group after 3 and 6 months of treatment; 3) dopamine levels in the study group were significantly higher than those in the control group after 6 months of completion of treatment, and γ-aminobutyric acid values and 5- serotonin values in the study group were significantly lower than those in the control group (p<0.05). CONCLUSIONS: Electroacupuncture combined with PP-LAI can partially improve the withdrawal symptoms and anxiety of methamphetamine addicts. This is a potential treatment for preventing relapse of withdrawal symptoms.

Counteracting TGM2 by a Fibroin peptide ameliorated Adriamycin-induced nephropathy via regulation of lipid metabolism through PANX1-PPAR α/PANK1 pathway.

Peptide drug discovery for the treatment of chronic kidney disease (CKD) has attracted much attention in recent years due to the urge to find novel drugs and mechanisms to delay the progression of the disease. In this study, we identified a novel short peptide (named YR-7, primary sequence 'YEVEDYR') from the natural Fibroin protein, and demonstrated that it significantly alleviated pathological renal changes in ADR-induced nephropathy. PANX1 was identified as the most notably upregulated component by RNA-sequencing. Further analysis showed that YR-7 alleviated the accumulation of lipid droplets via regulation of the lipid metabolism-related proteins PPAR α and PANK1. Using chemical proteomics, fluorescence polarization, microscale thermophoresis, surface plasmon resonance, and molecular docking, YR-7 was proven to directly bind to ß-barrel domains of TGM2 protein to inhibit lipid accumulation. TGM2 knockdown in vivo increased the protein levels of PPAR α and PANK1 while decreased the levels of fibrotic-related proteins to alleviate nephropathy. In vitro, overexpression TGM2 reversed the protective effects of YR-7. Co-immunoprecipitation indicated that TGM2 interacted with PANX1 to promote lipid deposition, and pharmacological inhibition or knockdown of PANX1 decreased the levels of PPAR α and PANK1 induced by ADR. Taken together, our findings revealed that TGM2-PANX1 interaction in promoting lipid deposition may be a new signaling in promoting ADR-induced nephropathy. And a novel natural peptide could ameliorate renal fibrosis through TGM2-PANX1-PPAR α/PANK1 pathway, which highlight the potential of it in the treatment of CKD.

GateView: A Multi-Omics Platform for Gene Feature Analysis of Virus Receptors within Human Normal Tissues and Tumors.

Viruses are obligate intracellular parasites that rely on cell surface receptor molecules to complete the first step of invading host cells. The experimental method for virus receptor screening is time-consuming, and receptor molecules have been identified for less than half of known viruses. This study collected known human viruses and their receptor molecules. Through bioinformatics analysis, common characteristics of virus receptor molecules (including sequence, expression, mutation, etc.) were obtained to study why these membrane proteins are more likely to become virus receptors. An in-depth analysis of the cataloged virus receptors revealed several noteworthy findings. Compared to other membrane proteins, human virus receptors generally exhibited higher expression levels and lower sequence conservation. These receptors were found in multiple tissues, with certain tissues and cell types displaying significantly higher expression levels. While most receptor molecules showed noticeable age-related variations in expression across different tissues, only a limited number of them exhibited gender-related differences in specific tissues. Interestingly, in contrast to normal tissues, virus receptors showed significant dysregulation in various types of tumors, particularly those associated with dsRNA and retrovirus receptors. Finally, GateView, a multi-omics platform, was established to analyze the gene features of virus receptors in human normal tissues and tumors. Serving as a valuable resource, it enables the exploration of common patterns among virus receptors and the investigation of virus tropism across different tissues, population preferences, virus pathogenicity, and oncolytic virus mechanisms.

Glucose uptake in trophoblasts of GDM mice is regulated by the AMPK-CLUT3 signaling pathway.

GDM, as a metabolic disease during pregnancy, regulates GLUT3 translocation by AMPK, thereby affecting glucose uptake in trophoblasts. It provides a new research idea and therapeutic target for alleviating intrauterine hyperglycemia in GDM. STZ was used to construct GDM mice, inject AICAR into pregnant mice, and observe fetal and placental weight; flow cytometry was employed for the detection of glucose uptake by primary trophoblast cells; immunofluorescence was applied to detect the localization of GLUT3 and AMPK in placental tissue; Cocofal microscope was used to detect the localization of GLUT3 in trophoblast cells;qRT-PCR and Western blot experiments were carried out to detect the expression levels of GLUT3 and AMPK in placental tissue; CO-IP was utilized to detect the interaction of GLUT3 and AMPK. Compared with the normal pregnancy group, the weight of the fetus and placenta of GDM mice increased (P < 0.001), and the ability of trophoblasts to take up glucose decreased (P < 0.001). In addition, AMPK activity in trophoblasts and membrane localization of GLUT3 in GDM mice were down-regulated compared with normal pregnant mice (P < 0.05). There is an interaction between GLUT3 and AMPK. Activating AMPK in trophoblasts can up-regulate the expression of GLUT3 membrane protein in trophoblasts of mice (P < 0.05) and increase the glucose uptake of trophoblasts (P < 0.05). We speculate that inhibition of AMPK activity in GDM mice results in aberrant localization of GLUT3, which in turn attenuates glucose uptake by placental trophoblast cells. AICAR activates AMPK to increase the membrane localization of GLUT3 and improve the glucose uptake capacity of trophoblasts.

Precise Regulation on the Bond Dissociation Energy of Exocyclic C-N Bonds in Various N-Heterocycle Electron Donors via Machine Learning.

Heterocycles with saturated N atoms (HetSNs) are widely used electron donors in organic light-emitting diode (OLED) materials. Their relatively low bond dissociation energy (BDE) of exocyclic C-N bonds has been closely related to material intrinsic stability and even device lifetime. Thus, it is imperative to realize fast prediction and precise regulation of those C-N BDEs, which demands a deep understanding of the relationship between the molecular structure and BDE. Herein, via machine learning (ML), we rapidly and accurately predicted C-N BDEs in various HetSNs and found that five-membered HetSNs (5-HetSNs) have much higher BDEs than almost all 6-HetSNs, except emerging boron-N blocks. Thorough analysis disclosed that high aromaticity is the foremost factor accounting for the high BDE of 5-HetSNs, and introducing intramolecular hydrogen-bond or electron-withdrawing moieties could also increase BDE. Importantly, the ML models performed well in various realistic OLED materials, showing great potential in characterizing material intrinsic stability for high-throughput virtual-screening and material design efforts.

Enhanced hydrodechlorination of 4-chlorophenol through carboxymethylcellulose-modified Pd/Fe nanosuspension synthesized by one-step methods.

Palladized iron (Pd/Fe) represents one of the most common modification strategies for nanoscale zero-valent iron (nZVI). Most studies prepared Pd/Fe by reducing iron salts and depositing Pd species on the surface of pre-synthesized nZVI, which can be called the two-step method. In this study, we proposed a one-step method to obtain Pd/Fe by the concurrent formation of Fe0 and Pd0 and investigated the effects of these two methods on 4-chlorophenol (4-CP) removal, with carboxymethylcellulose (CMC) coated as a surface modifier. Results indicated that the one-step method, not only streamlined the synthesis process, but also Pd/Fe-CMCone-step, synthesized by it, exhibited a higher 4-CP removal rate (97.9%) compared to the two-step method material Pd/Fe-CMCtwo-step (82.4%). Electrochemical analyses revealed that the enhanced activity of Pd/Fe-CMCone-step was attributed to its higher electron transfer efficiency and more available reactive species, active adsorbed hydrogen species (Hads*). Detection of intermediate products demonstrated that, under the influence of Pd/Fe-CMCone-step, the main route of 4-CP was through hydrodechlorination (HDC) to form phenol and H* was the main active specie, supported by EPR tests, quenching experiments and product analysis. Additionally, the effects of initial 4-CP concentration, initial pH, O2 concentration, anions such as Cl-, SO42-, HCO3-, and humic acid (HA) were also investigated. In conclusion, the results of this study suggest that Pd/Fe-CMCone-step, synthesized through the one-step method, is a convenient and efficient nZVI-modifying material suitable for the HDC of chlorinated organic compounds.

Efficacy and safety of drug-coated balloon for de novo lesions of large coronary arteries: Systematic review and meta-analysis of randomized controlled trials.

Background: Drug-coated balloon (DCB) is a novel approach to avoiding stent-related complications and has proven effective for the treatment of in-stent restenosis (ISR) and small vessels. However, its role in the treatment of de novo lesions in large vessels is less settled. Aims: To estimate the efficacy and safety of drug-coated balloon versus stent in the treatment of de novo lesions in large coronary arteries. Methods: We searched the literature until April 2023. We judged the safety of DCB based on major adverse cardiovascular events (MACEs), cardiac death, all-cause mortality, non-fatal myocardial infarction, target lesion revascularization (TLR), and bleeding event; and efficacy according to late lumen loss (LLL), minimum lumen diameter (MLD). We conducted subgroup analyses according to stent type and whether urgent PCI was required. Results: A total of 10 RCTs were included. Overall, LLL (mean difference (MD) = -0.19, 95 % confidence interval (CI): -0.32 to -0.06, P = 0.003) was lower in the DCB group than in the Stent arm. This effect was consistent in subgroup analysis regardless of stent type and disease type. In terms of safety indicators, there were no significant differences between DCB and stent. The subgroup analyses found that safety indicators showed no significant differences between DCB and drug-eluting stent (DES), but TLR was lower in the DCB than in the bare metal stent (BMS). Moreover, in ST-elevation myocardial infarction (STEMI), safety indicators and LLL showed no significant differences between DCB and DES, but MLD in the DCB was smaller. While in patients with excluded STEMI, MACE and TLR was lower in the DCB compared with the overall stent. Conclusions: DCB could be a promising alternative for treating de novo lesions in large coronary arteries with satisfactory efficacy and low risk, superior to BMS and not inferior to DES, with a trend toward lower late lumen loss.

MicroRNA397 promotes rice flowering by regulating the photorespiration pathway.

The precise timing of flowering plays a pivotal role in ensuring successful plant reproduction and seed production. This process is intricately governed by complex genetic networks that integrate internal and external signals. This study delved into the regulatory function of microRNA397 (miR397) and its target gene LACCASE-15 (OsLAC15) in modulating flowering traits in rice (Oryza sativa). Overexpression of miR397 led to earlier heading dates, decreased number of leaves on the main stem, and accelerated differentiation of the spikelet meristem. Conversely, overexpression of OsLAC15 resulted in delayed flowering and prolonged vegetative growth. Through biochemical and physiological assays, we uncovered that miR397-OsLAC15 had a profound impact on carbohydrate accumulation and photosynthetic assimilation, consequently enhancing the photosynthetic intensity in miR397-overexpressing rice plants. Notably, we identified that OsLAC15 is at least partially localized within the peroxisome organelle, where it regulates the photorespiration pathway. Moreover, we observed that a high CO2 concentration could rescue the late flowering phenotype in OsLAC15-overexpressing plants. These findings shed valuable insights into the regulatory mechanisms of miR397-OsLAC15 in rice flowering and provided potential strategies for developing crop varieties with early flowering and high-yield traits through genetic breeding.

Anatomic prognostic factors and their potential roles in refining M1 classification for de novo metastatic nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: To identify anatomic prognostic factors and their potential roles in refining M1 classification for de novo metastatic nasopharyngeal carcinoma (M1-NPC). MATERIALS AND METHODS: All M1-NPC treated with chemotherapy and/or radiotherapy between 2010 and 2019 from two centers (training and validation cohort) were included. The prognostic value of metastatic disease extent and involved organs for overall survival (OS) were assessed by several multivariable analyses (MVA) models. A new M1 classification was proposed and validated in a separate cohort who received immuno-chemotherapy. RESULTS: A total of 197 M1-NPC in the training and 307 in the validation cohorts were included for M1 subdivision study with median follow-up of 46 and 57 months. MVA model with "≤2 organs/≤5 lesions" as the definition of oligometastasis had the highest C-index (0.623) versus others (0.606-0.621). Patients with oligometastasis had better OS versus polymetastasis (hazard ratio [HR] 0.47/0.63) while liver metastases carried worse OS (HR 1.57/1.45) in MVA in the training/validation cohorts, respectively. We proposed to divide M1-NPC into M1a (oligometastasis without liver metastases) and M1b (liver metastases or polymetastasis) with 3-year OS of 66.5%/31.7% and 64.9%/35.0% in the training/validation cohorts, respectively. M1a subset had a better median progress-free survival (not reach vs. 17 months, p < 0.001) in the immuno-chemotherapy cohort (n = 163). CONCLUSION: Oligometastasis (≤2 organs/≤5 lesions) and liver metastasis are prognostic for M1-NPC. Subdivision of M1-NPC into M1a (oligometastasis without liver metastasis) and M1b (liver metastasis or polymetastasis) depicts the prognosis well in M1-NPC patients who received immuno-chemotherapy.

In vitro activities of contezolid (MRX-I) against drug-sensitive and drug-resistant Mycobacterium tuberculosis.

A novel oxazolidinone for the treatment of Mycobacterium tuberculosis has been developed, but the activity of contezolid (MRX-I) still needs to be clarified. In this study, we isolated Mycobacterium tuberculosis from 48 clinical patients with pulmonary tuberculosis. Roche drug susceptibility tests identified drug-sensitive and 39 drug-resistant M. tuberculosis isolates. Drug susceptibility assays indicated that MRX-I exhibited anti-Mycobacterium tuberculosis activity against both drug-sensitive and drug-resistant isolates, with an advantage against drug-resistant isolates. The results also showed that the anti-Mycobacterium tuberculosis activity was comparable to that of linezolid. IMPORTANCE Currently, Mycobacterium tuberculosis has exhibited increased drug resistance, leading to ineffective drug treatment in many patients with tuberculosis. Among the anti-Mycobacterium tuberculosis drugs, oxazolidinones have been gradually developed. Contezolid (MRX-I) has been newly developed in China with advantages versus the first oxazolidinone antibiotic approved by the Food and Drug Administration for clinical use, but the anti-M. tuberculosis activity needs to be further clarified. In this study, in vitro activities of MRX-I against M. tuberculosis were tested. The drug susceptibility assays indicated that MRX-I exhibited anti-M. tuberculosis activity comparable to that of linezolid, with an advantage against drug-resistant isolates.

Room-Temperature, Multigram-Scale Synthesis and Conversion Mechanism of Highly Luminescent Lead Sulfide Quantum Dots.

PbS quantum dots (QDs) are attractive near-infrared (NIR) materials, but traditional synthetic methods require inert atmosphere and/or high temperature. Herein we develop a facile, room-temperature synthetic route for in situ halide passivated PbS QDs through controllable reactions between lead halide, N,N'-diphenyl thiourea, and oleyamine (OLA) in toluene. Contrast experiments and theoretical calculations reveal that the OLA plays a bifunctional role as a mild base to initiate the formation of PbS monomers and as a dynamic ligand to control the crystallization of PbS QDs and further ligand exchange. The oleic acid-capped PbS QDs exhibit high photoluminescence quantum yields up to 45%. The scaled-up synthesis on multigram scales shows great batch-to-batch consistency. We further demonstrate high-power NIR light-emitting diodes using the PbS QDs as color converters, delivering NIR optical power of 9.2 mW at 160 mA. This work provides a simple and versatile synthetic route for high-quality PbS QDs and boosts the applications of NIR materials.

Longevity gene responsible for robust blue organic materials employing thermally activated delayed fluorescence.

The 3rd-Gen OLED materials employing thermally-activated delayed fluorescence (TADF) combine advantages of first two for high-efficiency and low-cost devices. Though urgently needed, blue TADF emitters have not met stability requirement for applications. It is essential to elucidate the degradation mechanism and identify the tailored descriptor for material stability and device lifetime. Here, via in-material chemistry, we demonstrate chemical degradation of TADF materials involves critical role of bond cleavage at triplet state rather than singlet, and disclose the difference between bond dissociation energy of fragile bonds and first triplet state energy (BDE-ET1) is linearly correlated with logarithm of reported device lifetime for various blue TADF emitters. This significant quantitative correlation strongly reveals the degradation mechanism of TADF materials have general characteristic in essence and BDE-ET1 could be the shared "longevity gene". Our findings provide a critical molecular descriptor for high-throughput-virtual-screening and rational design to unlock the full potential of TADF materials and devices.

LTBI-negative close contacts of tuberculosis are more likely to develop the disease: enlightenment and lessons from a cluster outbreak.

Background: Tuberculosis (TB) prevention and control among groups living together, such as students, workers, older adults in nursing homes, and prisoners, present many challenges due to their particular age and environmental factors, which can make them more susceptible to TB clusters with significant societal impact. This study aimed to evaluate a TB cluster outbreak epidemic in a university and provide suggestions for improving TB control strategies for groups living together. Methods: Pulmonary TB screening and close-contact investigation were conducted using acid-fast staining, sputum culture, GeneXpert testing, tuberculin skin testing (TST), interferon-gamma release assay (IGRA), and chest computed tomography (CT). GraphPad Prism 9.5.1 was utilized for data analysis. Collected epidemic data were comprehensively analyzed by rate comparison. Results: The TB cluster outbreak epidemic was identified with an index case confirmed positive. The initial screening was conducted on potential close contacts of the index case, and the TST's positive rate (diameter ≥ 5 mm) and strong positive rate (diameter ≥ 15 mm) among these close contacts were 65.60% (21/32) and 34.40% (11/32), respectively. Moreover, the latent TB infection (LTBI) rate (diameter ≥ 10 mm) was 43.75% (14/32), and the IGRA's positive rate was 9.30% (3/32). Chest CT scans did not reveal any abnormalities. Surprisingly, 5 of the close contacts developed active TB in the second screening, accompanied by changes from negative to positive TST and/or IGRA results, after 3 months of follow-up. Accordingly, we expanded the screening scope to include another 28 general contacts. We found that the positive rate (78.00%, 25/32), strong positive rate (50.00%, 16/32), and LTBI rate (62.50%, 20/32) of the 32 close contacts were significantly higher than those of the additional general contacts (28.00%, 8/28; 14.3%, 4/28; 25.00%, 7/28), as indicated by p < 0.05. Conclusion: In the event of an epidemic TB outbreak, it is essential to rapidly identify the source of infection and initiate timely screening of close contacts. The initial screening should be focused on individuals without LTBI, who are at higher risk of developing TB. In purified protein derivative-negative individuals living in groups, additional vaccination or revaccination with Bacille Calmette-Guérin may help prevent cluster outbreaks of TB.

Thermo-responsive polymer-modified metal-organic frameworks as soft-rigid enzyme-reactors for enhancement of enzymolysis efficiency using a controllable embedding protocol.

Enzyme immobilization is a suitable strategy to promote biosensing, biocatalysis and the industrial applications of biomacromolecules. Although considerable efforts have been devoted to the construction of metal-organic frameworks (MOFs)-based porous nano-reactors, their enzymolysis efficiency cannot be tuned by varying the external conditions due to the fixed conformation of the encapsulated enzymes. In this work, a controllable embedding protocol was developed based on the concept of stimuli-responsive polymer modified MOFs. Using MOFs as a rigid template for thermo-responsive polymer modification and consequently utilizing the polymer-MOFs complexes for enzyme (glucose oxidase, horseradish peroxidase, trypsin, cytochrome c, glutaminase) immobilization, different porous nano-reactors were fabricated. Most importantly, the polymer on the MOF surface exhibited good ability to form a "soft nest" at high temperature for inducing the confinement effect and further improving the enzymolysis efficiencies of the nano-reactors 3.75-37.7-fold. Moreover, a colorimetric sensing method was developed to detect serum glucose with the proposed nano-reactors. This strategy is highly versatile and suitable for diverse rigid MOFs modified with stimuli-responsive soft-polymer-nests and enzymes.

MRI-based deep learning model predicts distant metastasis and chemotherapy benefit in stage II nasopharyngeal carcinoma.

Chemotherapy remains controversial for stage II nasopharyngeal carcinoma because of its considerable prognostic heterogeneity. We aimed to develop an MRI-based deep learning model for predicting distant metastasis and assessing chemotherapy efficacy in stage II nasopharyngeal carcinoma. This multicenter retrospective study enrolled 1072 patients from three Chinese centers for training (Center 1, n = 575) and external validation (Centers 2 and 3, n = 497). The deep learning model significantly predicted the risk of distant metastases for stage II nasopharyngeal carcinoma and was validated in the external validation cohort. In addition, the deep learning model outperformed the clinical and radiomics models in terms of predictive performance. Furthermore, the deep learning model facilitates the identification of high-risk patients who could benefit from chemotherapy, providing useful additional information for individualized treatment decisions.

Zinc oxide nanoparticles have biphasic roles on Mycobacterium-induced inflammation by activating autophagy and ferroptosis mechanisms in infected macrophages.

The ability of zinc oxide nanoparticles (ZnONPs) to induce bacteriostasis in Mycobacterium tuberculosis (M. tb) and their roles in regulating the pathogenic activities of immune cells have been reported previously, but the specific mechanisms underlying these regulatory functions remain unclear. This work aimed to determine how ZnONPs play the antibacterial role against M. tb. In vitro activity assays were employed to determine the minimum inhibitory concentrations (MICs) of the ZnONPs against various strains of M. tb (BCG, H37Rv, and clinical susceptible MDR and XDR strains). The ZnONPs had MICs of 0.5-2 mg/L against all tested isolates. In addition, changes in the expression levels of autophagy and ferroptosis-related markers in BCG-infected macrophages exposed to ZnONPs were measured. BCG-infected mice that were administered ZnONPs were used to determine the ZnONPs functions in vivo. ZnONPs decreased the number of bacteria engulfed by the macrophages in a dose-dependent manner, while different doses of ZnONPs also affected inflammation in different directions. Although ZnONPs enhanced the BCG-induced autophagy of macrophages in a dose-dependent manner, only low doses of ZnONPs activated autophagy mechanisms by increasing the levels of pro-inflammatory factors. The ZnONPs also enhanced BCG-induced ferroptosis of macrophages at high doses. Co-administration of a ferroptosis inhibitor with the ZnONPs improved the anti-Mycobacterium activity of ZnONPs in an in vivo mouse model and alleviated acute lung injury caused by ZnONPs. Based on the above findings, we conclude that ZnONPs may act as potential antibacterial agents in future animal and clinical studies.