MACSPI enables tissue-selective proteomic and interactomic analyses in multicellular organisms.

Multicellular organisms are composed of many tissue types that have distinct morphologies and functions, which are largely driven by specialized proteomes and interactomes. To define the proteome and interactome of a specific type of tissue in an intact animal, we developed a localized proteomics approach called Methionine Analog-based Cell-Specific Proteomics and Interactomics (MACSPI). This method uses the tissue-specific expression of an engineered methionyl-tRNA synthetase to label proteins with a bifunctional amino acid 2-amino-5-diazirinylnonynoic acid in selected cells. We applied MACSPI in Caenorhabditis elegans, a model multicellular organism, to selectively label, capture, and profile the proteomes of the body wall muscle and the nervous system, which led to the identification of tissue-specific proteins. Using the photo-cross-linker, we successfully profiled HSP90 interactors in muscles and neurons and identified tissue-specific interactors and stress-related interactors. Our study demonstrates that MACSPI can be used to profile tissue-specific proteomes and interactomes in intact multicellular organisms.

Photo-ANA enables profiling of host-bacteria protein interactions during infection.

Bacterial pathogens rapidly change and adapt their proteome to cope with the environment in host cells and secrete effector proteins to hijack host targets and ensure their survival and proliferation during infection. Excessive host proteins make it difficult to profile pathogens' proteome dynamics by conventional proteomics. It is even more challenging to map pathogen-host protein-protein interactions in real time, given the low abundance of bacterial effectors and weak and transient interactions in which they may be involved. Here we report a method for selectively labeling bacterial proteomes using a bifunctional amino acid, photo-ANA, equipped with a bio-orthogonal handle and a photoreactive warhead, which enables simultaneous analysis of bacterial proteome reprogramming and pathogen-host protein interactions of Salmonella enterica serovar Typhimurium (S. Typhimurium) during infection. Using photo-ANA, we identified FLOT1/2 as host interactors of S. Typhimurium effector PipB2 in late-stage infection and globally profiled the extensive interactions between host proteins and pathogens during infection.

Development and application of the physiologically-based toxicokinetic (PBTK) model for ochratoxin A (OTA) in rats and humans.

Ochratoxin A (OTA) is a common fungal toxin frequently detected in food and human plasma samples. Currently, the physiologically based toxicokinetic (PBTK) model plays an active role in dose translation and can improve and enhance the risk assessment of toxins. In this study, the PBTK model of OTA in rats and humans was established based on knowledge of OTA-specific absorption, distribution, metabolism, and excretion (ADME) in order to better explain the disposition of OTA in humans and the discrepancies with other species. The models were calibrated and optimized using the available kinetic and toxicokinetic (TK) data, and independent test datasets were used for model evaluation. Subsequently, sensitivity analyses and population simulations were performed to characterize the extent to which variations in physiological and specific chemical parameters affected the model output. Finally, the constructed models were used for dose extrapolation of OTA, including the rat-to-human dose adjustment factor (DAF) and the human exposure conversion factor (ECF). The results showed that the unbound fraction (Fup) of OTA in plasma of rat and human was 0.02-0.04% and 0.13-4.21%, respectively. In vitro experiments, the maximum enzyme velocity (Vmax) and Michaelis-Menten constant (Km) of OTA in rat and human liver microsomes were 3.86 and 78.17 µg/g min-1, 0.46 and 4.108 µg/mL, respectively. The predicted results of the model were in good agreement with the observed data, and the models in rats and humans were verified. The PBTK model derived a DAF of 0.1081 between rats and humans, whereas the ECF was 2.03. The established PBTK model can be used to estimate short- or long-term OTA exposure levels in rats and humans, with the capacity for dose translation of OTA to provide the underlying data for risk assessment of OTA.

Negative serum (1,3) -ß-D-glucan has a low power to exclude Pneumocystis jirovecii pneumonia (PJP) in HIV-uninfected patients with positive qPCR.

OBJECTIVE: The current study evaluated the diagnostic performance of serum (1,3)-beta-D Glucan (BDG) in differentiating PJP from P. jirovecii-colonization in HIV-uninfected patients with P. jirovecii PCR-positive results. METHODS: This was a single-center retrospective study between 2019 and 2021. The diagnosis of PJP was based on the following criteria: detection of P. jirovecii in sputum or BAL specimen by qPCR or microscopy; Meet at least two of the three criteria: (1) have respiratory symptoms of cough and/or dyspnea, hypoxia; (2) typical radiological picture findings; (3) receiving a complete PJP treatment. After exclusion, the participants were divided into derivation and validation cohorts. The derivation cohort defined the cut-off value of serum BDG. Then, it was verified using the validation cohort. RESULTS: Two hundred and thirteen HIV-uninfected patients were enrolled, with 159 PJP and 54 P. jirovecii-colonized patients. BDG had outstanding specificity, LR, and PPV for PJP in both the derivation (90.00%, 8.900, and 96.43%) and the validation (91.67%, 9.176, and 96.30%) cohorts at ≥ 117.7 pg/mL. However, it had lower sensitivity and NPV in the derivation cohort (89.01% and 72.97%), which was even lower in the validation cohort (76.47% and 57.89%). Of note, BDG ≥ 117.7 pg/mL has insufficient diagnostic efficacy for PJP in patients with lung cancer, interstitial lung disease (ILD) and nephrotic syndrome. And although lymphocytes, B cells, and CD4+ T cells in PJP patients were significantly lower than those in P. jirovecii-colonized patients, the number and proportion of peripheral blood lymphocytes did not affect the diagnostic efficacy of serum BDG. CONCLUSIONS: Serum BDG ≥ 117.7 pg/mL could effectively distinguish P. jirovecii-colonization from infection in qPCR-positive HIV-uninfected patients with infectious diseases, solid tumors (excluding lung cancer), autoimmune or inflammatory disorders, and hematological malignancies. Of note, for patients with lung cancer, ILD, and nephrotic diseases, PJP should be cautiously excluded at BDG < 117.7 pg/mL.

Recovery of driving skills after endoscopy under propofol sedation: a prospective pilot study to assess the driving skills after endoscopic sedation using driving simulation.

BACKGROUND: Patients are recommended not to drive for at least the first 24 h after endoscopy with propofol sedation. However, the evidence underlying these recommendations is scarce. We hypothesized that after endoscopic procedures performed under propofol sedation, the subject's driving ability was restored in less than 24 h. METHODS: We prospectively enrolled thirty patients between 20 and 70 years possessing a legitimate driver's license scheduled for endoscopy at our hospital. The sample chosen was a convenience sample. Gastroscopy or colonoscopy was performed with propofol sedation. Before and after endoscopy, the investigator drove the subjects to the laboratory to assess their driving skills using a driving simulation system, which employs 3 driving scenarios designed by professional transportation researchers. The blood propofol concentration was estimated before endoscopy, and 2 and 4 h after endoscopy. The primary outcome was the time required for subjects to recover their driving ability after propofol sedation. The secondary outcome was the blood propofol concentration before and after endoscopic procedures under propofol anesthesia. RESULTS: Thirty volunteers participated in the study and 18 of them completed all the interventions. In the low-risk S-curve scene, the mean acceleration, lane deviation, and number of deviations from the path at baseline (0.016 cm/s2, 42.50 cm, and 0.83, respectively) were significantly less than that at post-2 h (0.029 cm/s2, P = 0.001; 53.80 cm, P = 0.014; 2.06, P = 0.022). In the moderate-(overtaking) and high-risk (emergency collision avoidance) scenes, the tested parameters at baseline and post-2 h were statistically comparable. In the low-, moderate-, and high-risk scenes the tested parameters at baseline and post-4 h were statistically comparable. The total range of propofol was 120-280 mg.The mean blood concentration of propofol at post-2 h was 0.81 ± 0.40 µg/mL, and at post-4 h was below the limit of detection. CONCLUSION: After endoscopy performed under propofol sedation, subjects' driving abilities were completely restored at 4 h when tested on a simulator.

Photo-Cross-Linking To Delineate Epigenetic Interactome.

Covalent modifications of DNA and histones are key cellular epigenetic marks to regulate gene functions. Most of these epigenetic marks are added or removed by corresponding enzymes known as writers and erasers, whose catalytic activities normally rely on the presence of cellular metabolites as cofactors. Epigenetic marks can either directly alter the chromatin structure and dynamics through changing the intra-/internucleosomal histone-histone and histone-DNA interactions or recruit readers that further bring in other proteins with chromatin-modifying/remodeling activities to reshape the local and regional chromatin organization. In these two ways, epigenetic modifications modulate diverse DNA-templated processes, such as gene transcription, DNA replication, and DNA damage repair. Therefore, elucidation of the regulatory mechanisms and biological significance of epigenetic marks requires the identification and characterization of the protein-protein, protein-nucleic acid, and protein-small molecule interactions that control the underlying epigenetic processes. Here, we review the recent advances in using photo-cross-linking strategies to interrogate the epigenetic interactome, focusing on the protein-protein interactions mediated by epigenetic marks in histone tails. We also discuss future directions of developing photo-cross-linking-based tools and methods toward the investigation of the binding events in nucleosomal/chromatinic contexts, and toward the in situ capture of the epigenetic interactome in live cells or even organisms.

Selective Targeting of AF9 YEATS Domain by Cyclopeptide Inhibitors with Preorganized Conformation.

YEATS domains are newly identified epigenetic "readers" of histone lysine acetylation (Kac) and crotonylation (Kcr). The malfunction of YEATS-Kac/Kcr interactions has been found to be involved in the pathogenesis of human diseases, such as cancer. These discoveries suggest that the YEATS domains are promising novel drug targets. We and others recently reported the development of YEATS domain inhibitors. Although these inhibitors have a general preference toward the AF9 and ENL YEATS domains, selective inhibitors targeting either YEATS domain are challenging to develop as these two proteins share a high structural similarity. In this study, we identified a proximal site outside the acyllysine-binding pocket that can differentiate AF9 YEATS from ENL YEATS. Combinatorial targeting of both the acyllysine pocket and this additional site by conformationally preorganized cyclopeptides enabled the selective inhibition of the AF9 YEATS domain. The most selective inhibitor, JYX-3, showed a 38-fold higher binding affinity toward AF9 YEATS over ENL YEATS. Further investigations indicated that JYX-3 could engage with AF9 in living cells, disrupt the YEATS-dependent chromatin recruitment of AF9, and suppress the transcription of AF9 target genes.

Structure-guided development of YEATS domain inhibitors by targeting π-π-π stacking.

Chemical probes of epigenetic 'readers' of histone post-translational modifications (PTMs) have become powerful tools for mechanistic and functional studies of their target proteins in normal physiology and disease pathogenesis. Here we report the development of the first class of chemical probes of YEATS domains, newly identified 'readers' of histone lysine acetylation (Kac) and crotonylation (Kcr). Guided by the structural analysis of a YEATS-Kcr complex, we developed a series of peptide-based inhibitors of YEATS domains by targeting a unique π-π-π stacking interaction at the proteins' Kcr recognition site. Further structure optimization resulted in the selective inhibitors preferentially binding to individual YEATS-containing proteins including AF9 and ENL with submicromolar affinities. We demonstrate that one of the ENL YEATS-selective inhibitors, XL-13m, engages with endogenous ENL, perturbs the recruitment of ENL onto chromatin, and synergizes the BET and DOT1L inhibition-induced downregulation of oncogenes in MLL-rearranged acute leukemia.

A comparison of reproductive isolation between two closely related oak species in zones of recent and ancient secondary contact.

BACKGROUND: Much of the debate over the evolutionary consequences of hybridization on genetic divergence and speciation results from the breakdown or reinforcement of reproductive barriers in secondary hybrid zones. Among hybrid populations established for different lengths of time following secondary contact, stronger reproductive barriers are generally expected to occur in zones with longer contact. However, in plants no detailed investigation of recent and ancient zones of secondary contact has been conducted despite the importance of such a comparative study. Here, we compare pre- and postzygotic reproductive barriers between two closely related oak species, Quercus mongolica and Q. liaotungensis, in such a situation. RESULTS: The recorded flowering times of both species overlapped in both contact zones. The fruit set at 10 and 30 days after interspecific hand pollination was not significantly lower than that after intraspecific pollination whenever Q. mongolica or Q. liaotungensis comprised the maternal parents in both populations. These results indicated that neither prezygotic phenological barriers nor interspecific incompatibility could have resulted in the reproductive isolation between the two species in both hybrid zones. However, the proportion of hybrid seeds produced by both species in the ancient zone was significantly lower than that recorded in the recent zone of secondary contact. In addition, the proportion of hybrid seeds simulated to form, assuming both random mating and an absence of postpollination barriers, was significantly higher than that detected in the ancient contact zone but not in the recent contact zone. These results suggest stronger early-acting postzygotic isolation between the two oak species in the ancient relative to the recent contact zone. CONCLUSIONS: Our comparative study demonstrated that postzygotic barriers during seed maturity were the main contributing factor to total reproductive isolation, particularly in the ancient contact zone, which aided species delimitation. In the recently formed secondary contact zone, pre- and postzygotic barriers were not well developed, and a high frequency of natural hybridization was evident. To our knowledge this study provides the first comparison of reproductive isolation between the ancient and recent secondary contact zones in plants and helps to clarify the evolutionary consequences of hybridization in a temporal context.

DKK1 inhibits breast cancer cell migration and invasion through suppression of ß-catenin/MMP7 signaling pathway.

BACKGROUND: DKK1 has been reported to act as a tumor suppressor in breast cancer. However, the mechanism of DKK1 inhibits breast cancer migration and invasion was still unclear. METHODS: Western blot and real time PCR was used to detect the expression of DKK1, ß-catenin and MMP7 in breast cancer cells. Wound scratch assay and transwell assay was employed to examine migration and invasion of breast cancer cell. RESULTS: DKK1 overexpression dramatically inhibits breast cancer cell migration and invasion. Knockdown of DKK1 promotes migration and invasion of breast cancer cells. DKK1 suppressed breast cancer cell migration and invasion through suppression of ß-catenin and MMP7 expression. XAV-939, an inhibitor of ß-catenin accumulation could reverse DKK1 silencing-induced MMP7 expression in breast cancer cells. Meanwhile, XAV-939 also could reverse the increase in the cell number invaded through Matrigel when DKK1 was knockdown. Furthermore, depletion of MMP7 also could reverse DKK1 knockdown-induced increase in the cell number invaded through Matrigel. CONCLUSIONS: DKK1 inhibits migration and invasion of breast cancer cell through suppression of ß-catenin/MMP7 pathway, our findings offered a potential alternative for breast cancer prevention and treatment.

Photo-lysine captures proteins that bind lysine post-translational modifications.

Post-translational modifications (PTMs) have key roles in regulating protein-protein interactions in living cells. However, it remains a challenge to identify these PTM-mediated interactions. Here we develop a new lysine-based photo-reactive amino acid, termed photo-lysine. We demonstrate that photo-lysine, which is readily incorporated into proteins by native mammalian translation machinery, can be used to capture and identify proteins that recognize lysine PTMs, including 'readers' and 'erasers' of histone modifications.

Genetically Encoded Photoaffinity Histone Marks.

Posttranslational modifications (PTMs) of lysine are crucial histone marks that regulate diverse biological processes. The functional roles and regulation mechanism of many newly identified lysine PTMs, however, remain yet to be understood. Here we report a photoaffinity crotonyl lysine (Kcr) analogue that can be genetically and site-specifically incorporated into histone proteins. This, in conjunction with the genetically encoded photo-lysine as a "control probe", enables the capture and identification of enzymatic machinery and/or effector proteins for histone lysine crotonylation.

Life history trait differentiation and local adaptation in invasive populations of Ambrosia artemisiifolia in China.

Local adaptation has been suggested to play an important role in range expansion, particularly among invasive species. However, the extent to which local adaptation affects the success of an invasive species and the factors that contribute to local adaptation are still unclear. This study aimed to investigate a case of population divergence that may have contributed to the local adaptation of invasive populations of Ambrosia artemisiifolia in China. Common garden experiments in seven populations indicated clinal variations along latitudinal gradients, with plants from higher latitudes exhibiting earlier flowering and smaller sizes at flowering. In reciprocal transplant experiments, plants of a northern Beijing origin produced more seeds at their home site than plants of a southern Wuhan origin, and the Wuhan-origin plants had grown taller at flowering than the Beijing-origin plants in Wuhan, which is believed to facilitate pollen dispersal. These results suggest that plants of Beijing origin may be locally adapted through female fitness and plants from Wuhan possibly locally adapted through male fitness. Selection and path analysis suggested that the phenological and growth traits of both populations have been influenced by natural selection and that flowering time has played an important role through its direct and indirect effects on the relative fitness of each individual. This study evidences the life history trait differentiation and local adaptation during range expansion of invasive A. artemisiifolia in China.

[Ethyl acetate-soluble chemical constituents from branch of Hypericum petiolulatum].

The stems and branches of Hypericum petiolulatum were extracted by alcohol and liquid-liquid extraction. Seven furofuran lignans were isolated from the ethyl acetate fraction of ethanol extract of H. petiolulatum by using silica gelchromatography, Sephadex LH-20 chromatography, medium-pressure liquid chromatography and preparative HPLC. Their structures were identified by the spectroscopic methods as pinoresinol (1), medioresinol (2), 8-acetoxypinoresinol (3), epipinoresinol (4), (+)-syringaresinol (5), (+)-1-hydroxysyringaresinol (6) and erythro-buddlenolE (7). All the isolates were firstly found in H. petiolulatum. In the bioassay, compound 7 showed remarkable antioxidative activity inhibiting Fe(+2)-cystine induced rat liver microsomal lipid peroxidation with inhibitory rate 38% at a concentration of 1 x 10(-6) mol · L(-1) (positive control Vit E with the inhibitory rate of 35% at the same concentration).

Advancements in ovarian cancer immunodiagnostics and therapeutics via phage display technology.

Ovarian cancer, ranking as the seventh most prevalent malignancy among women globally, faces significant challenges in diagnosis and therapeutic intervention. The difficulties in early detection are amplified by the limitations and inefficacies inherent in current screening methodologies, highlighting a pressing need for more efficacious diagnostic and treatment strategies. Phage display technology emerges as a pivotal innovation in this context, utilizing extensive phage-peptide libraries to identify ligands with specificity for cancer cell markers, thus enabling precision-targeted therapeutic strategies. This technology promises a paradigm shift in ovarian cancer management, concentrating on targeted drug delivery systems to improve treatment accuracy and efficacy while minimizing adverse effects. Through a meticulous review, this paper evaluates the revolutionary potential of phage display in enhancing ovarian cancer therapy, representing a significant advancement in combating this challenging disease. Phage display technology is heralded as an essential instrument for developing effective immunodiagnostic and therapeutic approaches in ovarian cancer, facilitating early detection, precision-targeted medication, and the implementation of customized treatment plans.

Advances and optimization strategies in bacteriophage therapy for treating inflammatory bowel disease.

In the advancement of Inflammatory Bowel Disease (IBD) treatment, existing therapeutic methods exhibit limitations; they do not offer a complete cure for IBD and can trigger adverse side effects. Consequently, the exploration of novel therapies and multifaceted treatment strategies provides patients with a broader range of options. Within the framework of IBD, gut microbiota plays a pivotal role in disease onset through diverse mechanisms. Bacteriophages, as natural microbial regulators, demonstrate remarkable specificity by accurately identifying and eliminating specific pathogens, thus holding therapeutic promise. Although clinical trials have affirmed the safety of phage therapy, its efficacy is prone to external influences during storage and transport, which may affect its infectivity and regulatory roles within the microbiota. Improving the stability and precise dosage control of bacteriophages-ensuring robustness in storage and transport, consistent dosing, and targeted delivery to infection sites-is crucial. This review thoroughly explores the latest developments in IBD treatment and its inherent challenges, focusing on the interaction between the microbiota and bacteriophages. It highlights bacteriophages' potential as microbiome modulators in IBD treatment, offering detailed insights into research on bacteriophage encapsulation and targeted delivery mechanisms. Particular attention is paid to the functionality of various carrier systems, especially regarding their protective properties and ability for colon-specific delivery. This review aims to provide a theoretical foundation for using bacteriophages as microbiome modulators in IBD treatment, paving the way for enhanced regulation of the intestinal microbiota.

DNA topoisomerase II is dispensable for oocyte meiotic resumption but is essential for meiotic chromosome condensation and separation in mice.

During mitosis, DNA topoisomerase II (TOP2) is required for sister chromatid separation. When TOP2 activity is inhibited, a decatenation checkpoint is activated by entangled chromatin. However, the functions of TOP2 in oocyte meiosis, particularly for homologous chromosome segregation during meiosis I, have not been investigated. In addition, it remains unknown if TOP2 inhibition activates a decatenation checkpoint at the G2/M transition in oocytes. In this study, we used mouse oocytes and specific inhibitors of TOP2 (ICRF-193 and etoposide) to investigate the role of TOP2 in meiosis. Our results indicated that an effective decatenation checkpoint did not exist in fully grown oocytes, as oocytes underwent the G2/M transition and reinitiated meiosis even when TOP2 activity was inhibited. However, oocytes treated with ICRF-193 had severe defects in chromosome condensation and homologous chromosome separation. Furthermore, condensed chromosomes failed to maintain their normal configurations in matured oocytes that were treated with ICRF-193. However, sister chromatid separation and subsequent chromosome decondensation during the exit from meiosis were not blocked by TOP2 inhibitors. These results indicated that TOP2 had a specific, crucial function in meiosis I. Thus, we identified important functions of TOP2 during oocyte maturation and provided novel insights into the decatenation checkpoint during meiosis.

[Correlation of ¹8F-FDG uptake with tumor-proliferating antigen Ki-67 expression in aggressive lymphoma].

OBJECTIVE: To investigate the correlation between ¹8F-FDG uptake in positron emission tomography/computed tomography imaging and tumor-proliferating antigen Ki-67 expression in aggressive lymphoma. METHODS: Data of ¹8F-FDG PET-CT imaging and immunohistochemical detection of Ki-67 expression of seventy-seven cases with initially diagnosed aggressive lymphoma were retrospectively analyzed. The intensity of ¹8F-FDG accumulation was determined by calculating the maximum standardized uptake value (SUVmax) and average standardized uptake value (SUVave). The average SUV at biopsy site (BxSUVave), SUVmax at biopsy site (BxSUVmax) and SUVmax at the highest tumor activity site of the body (BmSUVmax) were collected. RESULTS: The BmSUVmax, BxSUVmax, and BxSUVave were 13.4 ± 6.8, 11.9 ± 6.8 and 7.3 ± 4.4, respectively,and Ki-67 was (61.2 ± 20.4)% in the 77 aggressive lymphomas. The BmSUVmax was significantly higher than the BxSUVmax or BxSUVave (P < 0.05). The BmSUVmax, BxSUVmax and BxSUVave were positively correlated with the Ki-67 expression in aggressive lymphoma (P < 0.05). A positive correlation was revealed between the BxSUVmax and BmSUVmax (P < 0.05), and between the BxSUVmax and BxSUVave (P < 0.05). No significant correlation was found between the BmSUVmax or BxSUVmax and the Ki-67 in DLBCL (P > 0.05). A positive correlation was observed between the BmSUVmax or BxSUVmax and the Ki-67 expression in NK/T cell lymphoma (P < 0.05). CONCLUSION: The increasing trend of ¹8F-FDG uptake is correlated with the Ki-67 expression in aggressive lymphoma. The results of this study suggest that the metabolic information obtained by using BmSUVmax may help to compensate the limited sampling of histological examination at the biopsy site. Significant correlation in NK/T cell lymphoma suggests that the metabolic information from positron emission tomography-computed tomography may offer a useful parameter in the prognosis and management of this disease.

[Primary tumor SUVmax measured on (18)F-FDG PET-CT correlates with histologic grade and pathologic stage in non-small cell lung cancer].

OBJECTIVE: To assess the relationship between preoperative maximum standardized uptake value (SUVmax) measured on (18)F-FDG PET-CT and clinicopathologic parameters in patients with surgically resected non-small cell lung cancer (NSCLC). METHODS: A total of 540 patients (348 men and 192 women, mean age 60 ± 10 years) with histologically proven non-small cell lung cancer, who had undergone both preoperative (18)F-FDG PET-CT imaging and curative surgery in our institution from October 2006 to January 2013, were analyzed retrospectively in this study. Primary tumor (18)F-FDG uptake, measured as SUVmax corrected for lean body mass, was compared among different variables and correlated with tumor size, histologic grade and postoperative pathologic TNM stage. Histologic grade was categorized into three degrees, where grade I represents highly, grade II moderately and grade III poorly differentiated. Large cell carcinomas were all assessed as poorly differentiated (grade III). Pathologic stage was assigned according to the seventh AJCC TNM staging system. RESULTS: There were 344 adenocarcinomas (AC, non- BAC type), 146 squamous cell carcinomas (SCC), 28 bronchioloalveolar carcinomas (BAC), 10 adenosquamous carcinomas (ASC) and 12 other type carcinomas (OTC, including 6 large cell carcinomas, 5 sarcomatoid carcinomas and 1 lymphoepitheloid carcinoma); the SUVmax in ascending order was BAC (1.3 ± 1.1), AC (5.1 ± 3.4), ASC (8.5 ± 2.8), SCC (9.9 ± 4.6) and OTC (10.9 ± 5.1), respectively. There were 76 grade I, 251 grade II and 213 grade III; the SUVmax in ascending order was grade I (2.4 ± 2.2), grade II(5.9 ± 3.9), grade III (8.4 ± 4.4), respectively, and significant difference was identified among grade I, grade II and grade III (all P < 0.01). The SUV max was positively correlated with tumor size (r = 0.564, P < 0.01), histologic grade (r = 0.492, P < 0.01), T stage (r = 0.306, P < 0.01), N stage (r = 0.368, P < 0.01), and TNM stage (r = 0.437, P < 0.01). CONCLUSIONS: The preoperative SUV max of the primary tumor differed significantly among histologic types in NSCLC. There were positive correlations between SUV max and tumor size, histologic grade and pathologic stage. Our findings may suggest that a high SUVmax could be used to identify a high-risk population who would benefit most from adjuvant therapies.

Harnessing filamentous phages for enhanced stroke recovery.

Stroke poses a critical global health challenge, leading to substantial morbidity and mortality. Existing treatments often miss vital timeframes and encounter limitations due to adverse effects, prompting the pursuit of innovative approaches to restore compromised brain function. This review explores the potential of filamentous phages in enhancing stroke recovery. Initially antimicrobial-centric, bacteriophage therapy has evolved into a regenerative solution. We explore the diverse role of filamentous phages in post-stroke neurological restoration, emphasizing their ability to integrate peptides into phage coat proteins, thereby facilitating recovery. Experimental evidence supports their efficacy in alleviating post-stroke complications, immune modulation, and tissue regeneration. However, rigorous clinical validation is essential to address challenges like dosing and administration routes. Additionally, genetic modification enhances their potential as injectable biomaterials for complex brain tissue issues. This review emphasizes innovative strategies and the capacity of filamentous phages to contribute to enhanced stroke recovery, as opposed to serving as standalone treatment, particularly in addressing stroke-induced brain tissue damage.