Bacteroidota inhibit microglia clearance of amyloid-beta and promote plaque deposition in Alzheimer's disease mouse models.

The gut microbiota and microglia play critical roles in Alzheimer's disease (AD), and elevated Bacteroides is correlated with cerebrospinal fluid amyloid-ß (Aß) and tau levels in AD. We hypothesize that Bacteroides contributes to AD by modulating microglia. Here we show that administering Bacteroides fragilis to APP/PS1-21 mice increases Aß plaques in females, modulates cortical amyloid processing gene expression, and down regulates phagocytosis and protein degradation microglial gene expression. We further show that administering Bacteroides fragilis to aged wild-type male and female mice suppresses microglial uptake of Aß1-42 injected into the hippocampus. Depleting murine Bacteroidota with metronidazole decreases amyloid load in aged 5xFAD mice, and activates microglial pathways related to phagocytosis, cytokine signaling, and lysosomal degradation. Taken together, our study demonstrates that members of the Bacteroidota phylum contribute to AD pathogenesis by suppressing microglia phagocytic function, which leads to impaired Aß clearance and accumulation of amyloid plaques.

High expression of SRSF1 facilitates osteosarcoma progression and unveils its potential mechanisms.

BACKGROUND: SRSF1, a member of Serine/Arginine-Rich Splicing Factors (SRSFs), has been observed to significantly influence cancer progression. However, the precise role of SRSF1 in osteosarcoma (OS) remains unclear. This study aims to investigate the functions of SRSF1 and its underlying mechanism in OS. METHODS: SRSF1 expression level in OS was evaluated on the TCGA dataset, TAGET-OS database. qRT-PCR and Western blotting were employed to assess SRSF1 expression in human OS cell lines as well as the interfered ectopic expression states. The effect of SRSF1 on cell migration, invasion, proliferation, and apoptosis of OS cells were measured by transwell assay and flow cytometry. RNA sequence and bioinformatic analyses were conducted to elucidate the targeted genes, relevant biological pathways, and alternative splicing (AS) events regulated by SRSF1. RESULTS: SRSF1 expression was consistently upregulated in both OS samples and OS cell lines. Diminishing SRSF1 resulted in reduced proliferation, migration, and invasion and increased apoptosis in OS cells while overexpressing SRSF1 led to enhanced growth, migration, invasion, and decreased apoptosis. Mechanistically, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA) revealed that the biological functions of SRSF1 were closely associated with the dysregulation of the protein targeting processes, location of the cytosolic ribosome, extracellular matrix (ECM), and proteinaceous extracellular matrix, along with the PI3K-AKT pathway, Wnt pathway, and HIPPO pathway. Transcriptome analysis identified AS events modulated by SRSF1, especially (Skipped Exon) SE events and (Mutually exclusive Exons) MXE events, revealing potential roles of targeted molecules in mRNA surveillance, RNA degradation, and RNA transport during OS development. qRT-PCR confirmed that SRSF1 knockdown resulted in the occurrence of alternative splicing of SRRM2, DMKN, and SCAT1 in OS. CONCLUSIONS: Our results highlight the oncogenic role of high SRSF1 expression in promoting OS progression, and further explore the potential mechanisms of action. The significant involvement of SRSF1 in OS development suggests its potential utility as a therapeutic target in OS.

Constructing an Open-Structured J-Type ZnIn2S4/In(OH)3 Heterojunction for Photocatalytical Hydrogen Generation.

Constructing heterojunctions to separate photogenerated carriers is an effective strategy for improving the efficiency of photocatalytic reactions. A J-type heterojunction is a recently reported efficient anisotropic heterojunction. Herein, taking anisotropic ZnIn2S4 (ZIS) nanosheets as an example of a type-II heterojunction, we report for the first time the concept of open and closed structures (O and C structure) of J-type heterojunctions. A simple ammonia-post-treatment method was employed to prepare the O- and C-structured J-type ZnIn2S4/In(OH)3 (ZIS/IOH) heterojunctions. The O-structured J-type ZIS/IOH (OJ-ZIS/IOH) heterojunction exhibits a high hydrogen production activity, reaching 400 µmol·h-1, 2.67 times higher than that of pristine ZIS. However, the activity of the C-structured heterojunction (CJ-ZIS/IOH) is close to that of pristine ZIS. The findings emphasize the importance of the cooperation of photogenerated carrier separation and transport in J-type heterojunctions, providing insights into developing efficient heterojunction photocatalysts.

Effective Activation of Peroxymonosulfate by Oxygen Vacancy Induced Musa Basjoo Biochar to Degrade Sulfamethoxazole: Efficiency and Mechanism.

Biochar materials have garnered attention as potential catalysts for peroxymonosulfate (PMS) activation due to their cost-effectiveness, notable specific surface area, and advantageous structural properties. In this study, a suite of plantain-derived biochar (MBB-400, MBB-600, and MBB-800), possessing a well-defined pore structure and a substantial number of uniformly distributed active sites (oxygen vacancy, OVs), was synthesized through a facile calcination process at varying temperatures (400, 600, and 800 °C). These materials were designed for the activation of PMS in the degradation of sulfamethoxazole (SMX). Experimental investigations revealed that OVs not only functioned as enriched sites for pollutants, enhancing the opportunities for free radicals (•OH/SO4•-) and surface-bound radicals (SBRs) to attack pollutants, but also served as channels for intramolecular charge transfer leaps. This role contributed to a reduction in interfacial charge transfer resistance, expediting electron transfer rates with PMS, thereby accelerating the decomposition of pollutants. Capitalizing on these merits, the MBB-800/PMS system displayed a 61-fold enhancement in the conversion rate for SMX degradation compared to inactivated MBB/PMS system. Furthermore, the MBB-800 exhibited less cytotoxicity towards rat pheochromocytoma (PC12) cells. Hence, the straightforward calcination synthesis of MBB-800 emerges as a promising biochar catalyst with vast potential for sustainable and efficient wastewater treatment and environmental remediation.

Catalytically Active Carbon for Oxygen Reduction Reaction in Energy Conversion: Recent Advances and Future Perspectives.

The shortage and unevenness of fossil energy sources are affecting the development and progress of human civilization. The technology of efficiently converting material resources into energy for utilization and storage is attracting the attention of researchers. Environmentally friendly biomass materials are a treasure to drive the development of new-generation energy sources. Electrochemical theory is used to efficiently convert the chemical energy of chemical substances into electrical energy. In recent years, significant progress has been made in the development of green and economical electrocatalysts for oxygen reduction reaction (ORR). Although many reviews have been reported around the application of biomass-derived catalytically active carbon (CAC) catalysts in ORR, these reviews have only selected a single/partial topic (including synthesis and preparation of catalysts from different sources, structural optimization, or performance enhancement methods based on CAC catalysts, and application of biomass-derived CACs) for discussion. There is no review that systematically addresses the latest progress in the synthesis, performance enhancement, and applications related to biomass-derived CAC-based oxygen reduction electrocatalysts synchronously. This review fills the gap by providing a timely and comprehensive review and summary from the following sections: the exposition of the basic catalytic principles of ORR, the summary of the chemical composition and structural properties of various types of biomass, the analysis of traditional and the latest popular biomass-derived CAC synthesis methods and optimization strategies, and the summary of the practical applications of biomass-derived CAC-based oxidative reduction electrocatalysts. This review provides a comprehensive summary of the latest advances to provide research directions and design ideas for the development of catalyst synthesis/optimization and contributes to the industrialization of biomass-derived CAC electrocatalysis and electric energy storage.

The genetic association between hyperthyroidism and heart failure: a Mendelian randomization study.

Background and aims: Hyperthyroidism is an endocrine disease with multiple etiologies and manifestations. Heart failure (HF) is a common, costly, and deadly medical condition in clinical practice. Numerous studies have suggested that abnormal thyroid function can induce or aggravate the development of heart disease. However, no study has demonstrated a causal relationship between hyperthyroidism and heart failure. Therefore, the purpose of this study was to explore the causal link between hyperthyroidism and HF. Methods: Summary data for genetically predicted hyperthyroidism were obtained from a genetic association study. The data examined for genetically determined all-cause heart failure came from 218,208 individuals from the FinnGen Consortium. Two-sample Mendelian randomization (MR) analysis was used to estimate the causal link between hyperthyroidism and heart failure. Statistical analyses were conducted using the inverse variance-weighted, weighted median, simple median, weighted mode, MR-PRESSO (number of distribution = 5000), MR-Egger, and leave-one-out. Results: The results of the inverse-variance weighted analysis indicated a causal association between hyperthyroidism and an increased risk of all-cause heart failure (IVW: ß=0.048, OR=1.049, 95%CI: [1.013 to 1.087], P=0.007). Similarly, the weighted median approach demonstrated a positive correlation between hyperthyroidism and all-cause heart failure (OR=1.049, [95% CI, 1.001-1.100]; P=0.044). Additionally, no horizontal pleiotropy or heterogeneity was observed. The leave-one-out analysis revealed that the majority of the SNP-driven associations were not influenced by a single genetic marker. Conclusion: Our study observed a causal relationship between hyperthyroidism and all-cause heart failure. Hyperthyroidism may associate with heart failure genetically.

Optimal cut-off value for identifying objective response in patients with nasopharyngeal carcinoma after induction chemotherapy.

BACKGROUND: We aimed to establish the most suitable threshold for objective response (OR) in the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in patients with nasopharyngeal carcinoma (NPC). METHODS: According to RECIST 1.1, we retrospectively evaluated MR images of NPC lesions in patients before and after induction chemotherapy (IC). Restricted cubic spline and maximally selected rank statistics were used to determine the cut-off value. Survival rates and differences between groups were compared with Kaplan-Meier curves and log-rank tests. RESULTS: Of 1126 patients, 365 cases who received IC treatment were suitable for RECIST 1.1 evaluation. The 20% cut-off value maximized between-group differences according to maximally selected rank statistics. No difference in distant metastasis-free survival between OR and non-response groups was shown using the primary threshold of OR (30%), while it differed when 20% was employed. CONCLUSIONS: With an optimal cut-off value of 20%, RECIST may assist clinicians to accurately evaluate disease response in NPC patients.

Comparison of organic and synthetic amendments for poplar phytomanagement in copper and lead-contaminated calcareous soil.

Soil remediation can be achieved through organic and synthetic amendments, but the differences in the phytomanagement of trace metal-contaminated land are unclear. We conducted an outdoor microcosm experiment to simulate the effects of organic amendment citric acid and synthetic amendments EDTA and EGTA on poplar phytomanagement of copper (Cu)- and lead (Pb)-contaminated calcareous land at doses of 0, 1, 3, and 9 mmol kg-1. We found that soil-bioavailable Cu and Pb contents increased by 2.11-27.27 and 1.48-269 times compared to the control, respectively. Additionally, synthetic amendments had a long-lasting (within 25 days) effect on metal bioavailability relative to organic amendments. Consequently, organic amendments increased the root Cu and Pb contents by 2.68-48.61% and 6.60-49.51%, respectively, whereas synthetic amendments increased them by 65.94-260% and 12.50-103%. The Cu and Pb contents in the leaves were lower than those in the roots, and increased significantly by 47.04-179% and 237-601%, respectively, only under synthetic amendments. Interestingly, none of the amendments increased the Cu and Pb content in poplar stems (<5 mg kg-1), which remained within the normal range for terrestrial plants. Regardless of the type and addition level, the amendments did not affect poplar growth. Nevertheless, synthetic amendments caused a significant redistribution of metals (Cu: 22-32%; Pb: 23-53%) from the topsoil into the subsoil within the root zone at medium and high levels relative to organic amendments. Therefore, organic and synthetic amendments can assist poplar phytomanagement with a phytostabilization strategy for Cu- and Pb-contaminated calcareous land and obtain marketable wood biomass. Moreover, collecting leaf litter is crucial when using synthetic amendments at optimum concentration levels.

Enhancing Benzo[a]pyrene Degradation by Pantoea dispersa MSC14 through Biostimulation with Sodium Gluconate: Insights into Mechanisms and Molecular Regulation.

We investigated biostimulation as an effective strategy for enhancing the degradation efficiency of recalcitrant organic compounds, with MSC14 (a novel polycyclic aromatic hydrocarbon degrading bacterium Pantoea dispersa MSC14) as the study material. Here, we investigated the impact of sodium gluconate on MSC14-mediated degradation of B[a]p. This study focused on the application of sodium gluconate, a biostimulant, on MSC14, targeting Benzo[a]pyrene (B[a]p) as the model pollutant. In this study, the novel PAHs-degrading bacterium P. dispersa MSC14 demonstrated the capability to degrade 24.41% of B[a]p after 4 days. The addition of the selected sodium gluconate stimulant at a concentration of 4 g/L stimulated MSC14 to degrade 54.85% of B[a]p after 16 h. Intermediate metabolites were analyzed using gas chromatography-mass spectrometry to infer the degradation pathway. The findings indicated that sodium gluconate promoted the intracellular transport of B[a]p by MSC14, along with the secretion of biosurfactants, enhancing emulsification and solubilization capabilities for improved B[a]p dissolution and degradation. Further analysis through transmission electron microscopy (TEM) and scanning electron microscopy (SEM) revealed the formation of a biofilm by MSC14 and an increase in flagella as a response to B[a]p stress. Transcriptome profiling elucidated the interplay of quorum sensing systems, chemotaxis systems, and flagellar systems in the degradation mechanism. Additionally, the study uncovered the molecular basis of B[a]p transport, degradation pathways, metabolic changes, and genetic regulation. In summary, the addition of sodium gluconate promotes the degradation of B[a]p by P. dispersa MSC14, offering the advantages of being rapid, efficient, and cost-effective. This research provides an economically viable approach for the remediation of petroleum hydrocarbon pollution, with broad potential applications.

Incomplete transcripts dominate the Mycobacterium tuberculosis transcriptome.

Mycobacterium tuberculosis (Mtb) is a bacterial pathogen that causes tuberculosis (TB), an infectious disease that is responsible for major health and economic costs worldwide1. Mtb encounters diverse environments during its life cycle and responds to these changes largely by reprogramming its transcriptional output2. However, the mechanisms of Mtb transcription and how they are regulated remain poorly understood. Here we use a sequencing method that simultaneously determines both termini of individual RNA molecules in bacterial cells3 to profile the Mtb transcriptome at high resolution. Unexpectedly, we find that most Mtb transcripts are incomplete, with their 5' ends aligned at transcription start sites and 3' ends located 200-500 nucleotides downstream. We show that these short RNAs are mainly associated with paused RNA polymerases (RNAPs) rather than being products of premature termination. We further show that the high propensity of Mtb RNAP to pause early in transcription relies on the binding of the σ-factor. Finally, we show that a translating ribosome promotes transcription elongation, revealing a potential role for transcription-translation coupling in controlling Mtb gene expression. In sum, our findings depict a mycobacterial transcriptome that prominently features incomplete transcripts resulting from RNAP pausing. We propose that the pausing phase constitutes an important transcriptional checkpoint in Mtb that allows the bacterium to adapt to environmental changes and could be exploited for TB therapeutics.

Developing a machine learning-based short form of the positive and negative syndrome scale.

BACKGROUND AND HYPOTHESIS: The Positive and Negative Syndrome Scale (PANSS) consists of 30 items and takes up to 50 minutes to administer and score. Therefore, this study aimed to develop and validate a machine learning-based short form of the PANSS (PANSS-MLSF) that reproduces the PANSS scores. Moreover, the PANSS-MLSF estimated the removed-item scores. STUDY DESIGN: The PANSS-MLSF was developed using an artificial neural network, and the removed-item scores were estimated using the eXtreme Gradient Boosting classifier algorithm. The reliability of the PANSS-MLSF was examined using Cronbach's alpha. The concurrent validity was examined by the association (Pearson's r) between the PANSS-MLSF and the PANSS. The convergent validity was examined by the association (Pearson's r) between the PANSS-MLSF and the Clinical Global Impression-Severity, Mini-Mental State Examination, and Lawton Instrumental Activities of Daily Living Scale. The agreement of the estimated removed-item scores with their original scores was examined using Cohen's kappa. STUDY RESULTS: Our analysis included data from 573 patients with moderate severity. The two versions of the PANSS-MLSF comprised 15 items and 9 items were proposed. The PANSS-MLSF scores were similar to the PANSS scores (mean squared error=2.6-24.4 points). The reliability, concurrent validity, and convergent validity of the PANSS-MLSF were good. Moderate to good agreement between the estimated removed-item scores and the original item scores was found in 60% of the removed items. CONCLUSION: The PANSS-MLSF offers a viable way to reduce PANSS administration time, maintain score comparability, uphold reliability and validity, and even estimate scores for the removed items.

Biomass-Derived Catalytically Active Carbon Materials for the Air Electrode of Zn-air Batteries.

Given the growing environmental and energy problems, developing clean, renewable electrochemical energy storage devices is of great interest. Zn-air batteries (ZABs) have broad prospects in energy storage because of their high specific capacity and environmental friendliness. The unavailability of cheap air electrode materials and effective and stable oxygen electrocatalysts to catalyze air electrodes are main barriers to large-scale implementation of ZABs. Due to the abundant biomass resources, self-doped heteroatoms, and unique pore structure, biomass-derived catalytically active carbon materials (CACs) have great potential to prepare carbon-based catalysts and porous electrodes with excellent performance for ZABs. This paper reviews the research progress of biomass-derived CACs applied to ZABs air electrodes. Specifically, the principle of ZABs and the source and preparation method of biomass-derived CACs are introduced. To prepare efficient biomass-based oxygen electrocatalysts, heteroatom doping and metal modification were introduced to improve the efficiency and stability of carbon materials. Finally, the effects of electron transfer number and H2 O2 yield in ORR on the performance of ZABs were evaluated. This review aims to deepen the understanding of the advantages and challenges of biomass-derived CACs in the air electrodes of ZABs, promote more comprehensive research on biomass resources, and accelerate the commercial application of ZABs.

Label-Free In Vivo Monitoring of Lipid Droplets for Real-Time Assessment of Adipose Activator-Induced Tumor Suppression.

To enhance our comprehension of the fundamental mechanisms driving tumor metabolism and metastasis, it is essential to dynamically monitor intratumoral lipid droplet (LD) and collagen processes in vivo. Traditional LD analysis in tumors predominantly relies on observations of in vitro cells or tissue slices, which unfortunately hinder real-time insights into the dynamic behavior of LDs during in vivo tumor progression. In this study, we developed a dual-modality imaging technique that combines coherent anti-Stokes Raman scattering (CARS) and second-harmonic generation (SHG) microscopy for in vivo monitoring of tumor LDs and collagen alterations, assisted by a murine breast cancer 4T1 cell-based dorsal skinfold window. Specifically, we accomplished real-time observations and quantitative analysis of the LD size, density, and collagen alignment within living tumors through CARS/SHG imaging. Additionally, our findings demonstrate that real-time LD monitoring provides a valuable means of assessing the efficacy of anticancer drugs in vivo. We evaluated the impact of adipose activators on lipid metabolism, oxidative stress, and tumor suppression by monitoring changes in LD size and density. Overall, this study highlights the potential of dual-modality CARS/SHG microscopy as a sensitive and flexible tool for antitumor therapeutic strategies.

Fe, N-Inducing Interfacial Electron Redistribution in NiCo Spinel on Biomass-Derived Carbon for Bi-functional Oxygen Conversion.

Herein, an interfacial electron redistribution is proposed to boost the activity of carbon-supported spinel NiCo2O4 catalyst toward oxygen conversion via Fe, N-doping strategy. Fe-doping into octahedron induces a redistribution of electrons between Co and Ni atoms on NiCo1.8Fe0.2O4@N-carbon. The increased electron density of Co promotes the coordination of water to Co sites and further dissociation. The generation of proton from water improves the overall activity for the oxygen reduction reaction (ORR). The increased electron density of Ni facilitates the generation of oxygen vacancies. The Ni-VO-Fe structure accelerates the deprotonation of *OOH to improve the activity toward oxygen evolution reaction (OER). N-doping modulates the electron density of carbon to form active sites for the adsorption and protonation of oxygen species. Fir wood-derived carbon endows catalyst with an integral structure to enable outstanding electrocatalytic performance. The NiCo1.8Fe0.2O4@N-carbon express high half-wave potential up to 0.86 V in ORR and low overpotential of 270 mV at 10 mA cm-2 in OER. The zinc-air batteries (ZABs) assembled with the as-prepared catalyst achieve long-term cycle stability (over 2000 cycles) with peak power density (180 mWcm-2). Fe, N-doping strategy drives the catalysis of biomass-derived carbon-based catalysts to the highest level for the oxygen conversion in ZABs.

CDYL for infrared and visible light image dense small object detection.

To address the phenomenon of many small and hard-to-detect objects in infrared and visible light images, we propose an object detection algorithm CDYL (Convolution to Fully Connect-ed-Deformable Convolution You only Look once) based on the CFC-DC (Convolution to Fully Connected-Deformable Convolution) module. The core operator of CDYL is CFC-DC, making our model not only have a large effective receptive field in infrared and visible light images, but also have adaptive spatial aggregation conditioned by input and task information. As a result, the CDYL reduces the strict inductive bias of traditional CNNs and has long-range dependence for large kernel convolution as well as adaptive spatial aggregation, deeply mining of edge and correlation information in images to enhance sensitivity to small objects, thereby improving performance in dense small object detection tasks. In order to improve the ability of the CFC-DC module to perceive the detailed information of the image, we use the Mish activation function, which has a wider minima which improves the generalization. The effectiveness as well as the generalization of CDYL is evaluated on an infrared image dataset and an UAV image dataset, and it is compared with other state-of-the-art object detection algorithms. Compared to the baseline network YOLOv8l, our model achieved a 3.0% improvement in mAP0.5 in infrared image detection tasks and a 1.1% improvement in mAP0.5 in visible light image detection tasks. The experimental results show that the proposed algorithm achieves superior average precision values on both infrared and visible light images, while maintaining a light weight. Code is publicly available at https://github.com/yangzhu1/CDYL .

Value of radiological depth of invasion in non-pT4 Oral tongue squamous cell carcinoma: implication for preoperative MR T-staging.

OBJECTIVE: The prognostic stratification for oral tongue squamous cell carcinoma (OTSCC) is heavily based on postoperative pathological depth of invasion (pDOI). This study aims to propose a preoperative MR T-staging system based on tumor size for non-pT4 OTSCC. METHODS: Retrospectively, 280 patients with biopsy-confirmed, non-metastatic, pT1-3 OTSCC, treated between January 2010 and December 2017, were evaluated. Multiple MR sequences, including axial T2-weighted imaging (WI), unenhanced T1WI, and axial, fat-suppressed coronal, and sagittal contrast-enhanced (CE) T1WI, were utilized to measure radiological depth of invasion (rDOI), tumor thickness, and largest diameter. Intra-class correlation (ICC) and univariate and multivariate analyses were used to evaluate measurement reproducibility, and factors' significance, respectively. Cutoff values were established using an exhaustive method. RESULTS: Intra-observer (ICC = 0.81-0.94) and inter-observer (ICC = 0.79-0.90) reliability were excellent for rDOI measurements, and all measurements were significantly associated with overall survival (OS) (all p < .001). Measuring the rDOI on axial CE-T1WI with cutoffs of 8 mm and 12 mm yielded an optimal MR T-staging system for rT1-3 disease (5-year OS of rT1 vs rT2 vs rT3: 94.0% vs 72.8% vs 57.5%). Using multivariate analyses, the proposed T-staging exhibited increasingly worse OS (hazard ratio of rT2 and rT3 versus rT1, 3.56 [1.35-9.6], p = .011; 4.33 [1.59-11.74], p = .004; respectively), which outperformed pathological T-staging based on nonoverlapping Kaplan-Meier curves and improved C-index (0.682 vs. 0.639, p < .001). CONCLUSIONS: rDOI is a critical predictor of OTSCC mortality and facilitates preoperative prognostic stratification, which should be considered in future oral subsite MR T-staging. CLINICAL RELEVANCE STATEMENT: Utilizing axial CE-T1WI, an MR T-staging system for non-pT4 OTSCC was developed by employing rDOI measurement with optimal thresholds of 8 mm and 12 mm, which is comparable with pathological staging and merits consideration in future preoperative oral subsite planning. KEY POINTS: • Tumor morphology, measuring sequences, and observers could impact MR-derived measurements and compromise the consistency with histology. • MR-derived measurements, including radiological depth of invasion (rDOI), tumor thickness, and largest diameter, have a prognostic impact on OS (all p < .001). • rDOI with cutoffs of 8 mm and 12 mm on axial CE-T1WI is an optimal predictor of OS and could facilitate risk stratification in non-pT4 OTSCC disease.

Beyond antibiotic resistance: The whiB7 transcription factor coordinates an adaptive response to alanine starvation in mycobacteria.

Pathogenic mycobacteria are a significant cause of morbidity and mortality worldwide. The conserved whiB7 stress response reduces the effectiveness of antibiotic therapy by activating several intrinsic antibiotic resistance mechanisms. Despite our comprehensive biochemical understanding of WhiB7, the complex set of signals that induce whiB7 expression remain less clear. We employed a reporter-based, genome-wide CRISPRi epistasis screen to identify a diverse set of 150 mycobacterial genes whose inhibition results in constitutive whiB7 expression. We show that whiB7 expression is determined by the amino acid composition of the 5' regulatory uORF, thereby allowing whiB7 to sense amino acid starvation. Although deprivation of many amino acids can induce whiB7, whiB7 specifically coordinates an adaptive response to alanine starvation by engaging in a feedback loop with the alanine biosynthetic enzyme, aspC. These findings describe a metabolic function for whiB7 and help explain its evolutionary conservation across mycobacterial species occupying diverse ecological niches.

Expression and Clinical Significance of CD30 and CD56 in Lymphoblastic Lymphoma: A Retrospective Analysis on Paraffin-Embedded Tissues by Immunohistochemistry.

Background: We evaluated CD30 and CD56 expression in lymphoblastic lymphoma (LBL) and correlated the results with clinicopathological features and prognosis. Methods: Immunohistochemical (IHC) staining was performed on 85 formalin-fixed paraffin-embedded LBL specimens using two CD30 clones and one CD56 antibody clone. Results: Weak and diffuse expression of CD30 was expressed in 4.7% (clone Ber-H2) or 14.1% (clone EPR4102) in LBL, while CD56 was expressed in 24.7%. CD30 and CD56 expression correlated with lactate dehydrogenase levels. CD56-positive expression was closely associated with an unfavorable prognosis. Although CD30 expression exhibited a trend toward poorer overall survival, it did not reach statistical significance. Conclusion: CD56 is a potential negative prognostic marker. These findings suggest that CD30 and CD56 targeted therapies could be potential therapeutic targets for LBL patients.

Refining the 8th edition TNM classification for EBV related nasopharyngeal carcinoma.

The AJCC/UICC TNM classification describes anatomic extent of tumor progression and guides treatment decisions. Our comprehensive analysis of 8,834 newly diagnosed patients with non-metastatic Epstein-Barr virus related nasopharyngeal carcinoma (NPC) from six Chinese centers indicates certain limitations in the current staging system. The 8th edition of the AJCC/UICC TNM classification inadequately differentiates patient outcomes, particularly between T2 and T3 categories and within the N classification. We propose reclassifying cases of T3 NPC with early skull-base invasion as T2, and elevating N1-N2 cases with grade 3 image-identified extranodal extension (ENE) to N3. Additionally, we suggest combining T2N0 with T1N0 into a single stage IA. For de novo metastatic (M1) NPC, we propose subdivisions of M1a, defined by 1-3 metastatic lesions without liver involvement, and M1b, characterized by >3 metastatic lesions or liver involvement. This proposal better reflects responses of NPC patients to the up-to-date treatments and their evolving risk profiles.

Multipath diffusion process and spatial accumulation simulation of Cd in lead-zinc mining areas.

This study combined process simulation and actual measurement to construct a multipath diffusion and spatial accumulation model of Cd in a typical lead-zinc mining area through accuracy and root mean square error(RMSE) analysis. The results indicated that (1) the diffusion of Cd was in a quadratic inverse proportional relationship with the distance from the pollution source within watershed. The average annual atmospheric Cd sedimentation in study area was 0.71 * 10-6 g and the contribution of runoff diffusion to Cd exceeded 80%. (2) With the increase in the concentration range of Cd content (k) carried by unit runoff sediment, the model accuracy and RMSE showed decreasing trends. However, when the lower and upper limits of k were 10% and 90%, the model accuracy reached 75%. (3) Two sub-watersheds with same dominant wind direction but different runoff directions were selected to verify the model accuracy, indicating that the model construction method can precisely simulate the spatial accumulation of Cd in similar mining areas. The results provide a scientific basis for the prevention of heavy metal diffusion in lead-zinc mines. Future research should focus on the migration pathways of heavy metals through vertical infiltration caused by rainfall to further optimise the model structure and accuracy.