In Situ Construction of CdS/g-C3N4 Heterojunctions in Spent Thiolation@Wood-Aerogel for Efficient Excitation Peroxymonosulfate to Degradation Tetracycline.

Pollutant treatment, hazardous solid waste conversion, and biomass resource utilization are significant topics in environmental pollution control, and simultaneously achieving them is challenging. Herein, we developed a "from waste absorbent to effective photocatalyst" upcycle strategy for nontoxic conversion of Cd(II) adsorbed on thiolation@wood-aerogel (TWA) into CdS/g-C3N4 heterojunctions through the in situ chemical deposition high-temperature carbonization combined conversion method to overcome the above problems simultaneously. We used Schiff base reaction to graft l-cysteine into dialdehyde@wood-aerogel to prepare TWA with a high Cd(II) adsorption capacity (600 mg/L, 294.66 mg/g). Subsequently, the spent Cd(II)-loaded-TWA was used as a substrate for in situ construction of Cd(II) into CdS/g-C3N4 heterojunction for activating peroxymonosulfate (PMS) under simulated sunlight [simulated solar light (SSL)], achieving efficient tetracycline (TC) degradation (20 mg/L, 95.32%). The Langmuir and pseudo-second-order models indicate single-layer chemical adsorption of Cd(II) on the TWA adsorption process. In the PMS/SSL system, CdS/g-C3N4@TWA efficiently and rapidly degraded TC via an adsorption-photocatalytic synergistic degradation mechanism. The used CdS/g-C3N4@TWA has a good biocompatibility. This study proposed design and preparation of a new type of wood aerogel absorbent and provided a novel upcycling strategy for innovative use of the spent waste adsorbent.

Global research landscape and trends of cancer stem cells from 1997 to 2023: A bibliometric analysis.

Cancer stem cells (CSCs) are a subset of cells with self-renewal ability and tumor generating potential. Accumulated evidence has revealed that CSCs were shown to contribute to tumorigenesis, metastasis, recurrence and resistance to chemoradiotherapy. Therefore, CSCs were regarded as promising therapeutic targets in cancer. This study is the first to reveal the development process, research hotspots, and trends of entire CSCs research field through bibliometric methods. All relevant publications on CSCs with more than 100 citations (notable papers) and the 100 most cited papers (top papers) during 1997 to 2023 were extracted and analyzed. Cancer research published the largest number of papers (184 papers). The USA accounted for the most publications (1326 papers). Rich, JN was the author with the most publications (56 papers) and the highest M-index (3.111). The most contributive institution was the University of Texas System (164 papers). Before 2007, research mainly focused on the definition and recognition of CSCs. Between 2007 and 2016, with the emergence of the terms such as "sonic hedgehog," "metabolism," "oxidative phosphorylation," and "epithelial mesenchymal transition," research began to shift toward exploring the mechanisms of CSCs. In 2016, the focus transitioned to the tumor microenvironment and the ecological niches. The analysis of papers published in major journals since 2021 showed that "transcription," "inhibition," and "chemoresistance" emerged as new focused issues. In general, the research focus has gradually shifted from basic biology to clinical transformation. "Tumor microenvironment" and "chemo-resistance" should be given more attention in the future.

Chemical and Geological Properties of Shale Gas: In Situ Desorption of Lower Cambrian Niutitang Shale in the Micangshan Tectonic Zone of South Shaanxi, China.

Shale gas was recently found in the Lower Cambrian Niutitang Formation (LCNF) of the Micangshan tectonic zone of south Shaanxi (MTZSS), but not in commercial quantities. To determine the laws governing the generation, enrichment, and desorption of shale gases in overmatured shale strata in the LCNF of MTZSS, we carried out in situ desorption experiments on nine shale core samples and got 168 desorbed gas samples at different phases of desorption. Also measured were the chemical and carbon isotopic compositions of these desorbed gas samples and the geochemical parameters of the shale core samples. CH4 was the predominant hydrocarbon shale gas identified in the 82.06-98.48% range, suggesting that the gases were mainly dry. The nonhydrocarbon gases found were CO2 and H2. The CH4 content of the desorbed gas samples dropped continuously during desorption, lowering the dryness index to 98.48 and 92.26% of the first and last desorbed shale gas, respectively. The change in the gas ratio during shale gas desorption proved that the adsorbability of the LCNF to the various gases follows the trend H2 > CO2 > C2H6 > CH4 > He. Further, δ13C2H6 and δ13CH4 become heavier during desorption, showing isotopic fractionation arising from the desorption-diffusion coeffect. As the desorption temperature increases, the value of δ13CH4 increases because 12CH4 is more sensitive to temperature than 13CH4, so it is with the ethane. Similar to the LCNF shale gas in other areas of China, the desorbed shale gases are characteristic of carbon isotope reversal (CIR) (δ13CH4 > δ13C2H6). The cracking of the residual soluble organic matter at the high overmaturity stage mixed with the cracking of kerogen at the early stage of maturation, causing CIR. Furthermore, the desorbed gas content was proportionally and inversely related to the CIR degree and final dryness index of the desorbed gas, respectively. Moreover, the carbon isotope fractionation degree of CH4 and δ13C1 of the last desorbed gas correlated positively with the desorbed gas content and the desorbed time of the gas. In conclusion, the four parameters are effective parameters for identifying shale gas sweet spots.

A benchmarking framework for the accurate and cost-effective detection of clinically-relevant structural variants for cancer target identification and diagnosis.

BACKGROUND: Accurate clinical structural variant (SV) calling is essential for cancer target identification and diagnosis but has been historically challenging due to the lack of ground truth for clinical specimens. Meanwhile, reduced clinical-testing cost is the key to the widespread clinical utility. METHODS: We analyzed massive data from tumor samples of 476 patients and developed a computational framework for accurate and cost-effective detection of clinically-relevant SVs. In addition, standard materials and classical experiments including immunohistochemistry and/or fluorescence in situ hybridization were used to validate the developed computational framework. RESULTS: We systematically evaluated the common algorithms for SV detection and established an expert-reviewed SV call set of 1,303 tumor-specific SVs with high-evidence levels. Moreover, we developed a random-forest-based decision model to improve the true positive of SVs. To independently validate the tailored 'two-step' strategy, we utilized standard materials and classical experiments. The accuracy of the model was over 90% (92-99.78%) for all types of data. CONCLUSION: Our study provides a valuable resource and an actionable guide to improve cancer-specific SV detection accuracy and clinical applicability.

Novel subsets of peripheral immune cells associated with promoting stroke recovery in mice.

AIMS: Peripheral immune cells infiltrating into the brain trigger neuroinflammation after an ischemic stroke. Partial immune cells reprogram their function for neural repair. Which immune cells promote ischemic brain recovery needs further identification. METHODS: We performed single-cell transcriptomic profiling of CD45high immune cells isolated from the ischemic hemisphere at subacute (5 days) and chronic (14 days) stages after ischemic stroke. RESULTS: A subset of phagocytic macrophages was associated with neuron projection regeneration and tissue remodeling. We also identified a unique type of T cells with highly expressed macrophage markers, including C1q, Apoe, Hexb, and Fcer1g, which showed high abilities in tissue remodeling, myelination regulation, wound healing, and anti-neuroinflammation. Moreover, natural killer cells decreased cytotoxicity and increased energy and metabolic function in the chronic stage after ischemic stroke. Two subgroups of neutrophils upregulated CCL signals to recruit peripheral immune cells and released CXCL2 to keep self-recruiting at the chronic stage. CONCLUSIONS: We identified subsets of peripheral immune cells that may provide potential therapeutic targets for promoting poststroke recovery.

Modulating a prebiotic food source influences inflammation and immune-regulating gut microbes and metabolites: insights from the BE GONE trial.

BACKGROUND: Accessible prebiotic foods hold strong potential to jointly target gut health and metabolic health in high-risk patients. The BE GONE trial targeted the gut microbiota of obese surveillance patients with a history of colorectal neoplasia through a straightforward bean intervention. METHODS: This low-risk, non-invasive dietary intervention trial was conducted at MD Anderson Cancer Center (Houston, TX, USA). Following a 4-week equilibration, patients were randomized to continue their usual diet without beans (control) or to add a daily cup of study beans to their usual diet (intervention) with immediate crossover at 8-weeks. Stool and fasting blood were collected every 4 weeks to assess the primary outcome of intra and inter-individual changes in the gut microbiome and in circulating markers and metabolites within 8 weeks. This study was registered on ClinicalTrials.gov as NCT02843425, recruitment is complete and long-term follow-up continues. FINDINGS: Of the 55 patients randomized by intervention sequence, 87% completed the 16-week trial, demonstrating an increase on-intervention in diversity [n = 48; linear mixed effect and 95% CI for inverse Simpson index: 0.16 (0.02, 0.30); p = 0.02] and shifts in multiple bacteria indicative of prebiotic efficacy, including increased Faecalibacterium, Eubacterium and Bifidobacterium (all p < 0.05). The circulating metabolome showed parallel shifts in nutrient and microbiome-derived metabolites, including increased pipecolic acid and decreased indole (all p < 0.002) that regressed upon returning to the usual diet. No significant changes were observed in circulating lipoproteins within 8 weeks; however, proteomic biomarkers of intestinal and systemic inflammatory response, fibroblast-growth factor-19 increased, and interleukin-10 receptor-α decreased (p = 0.01). INTERPRETATION: These findings underscore the prebiotic and potential therapeutic role of beans to enhance the gut microbiome and to regulate host markers associated with metabolic obesity and colorectal cancer, while further emphasizing the need for consistent and sustainable dietary adjustments in high-risk patients. FUNDING: This study was funded by the American Cancer Society.

Integrated multiplex network based approach reveled CC and CXC chemokines associated key biomarkers in colon adenocarcinoma patients.

Colon adenocarcinoma (COAD) is a prevalent and aggressive form of cancer that necessitates the identification of robust biomarkers for early diagnosis and treatment. Therefore, this project was launched to identify a few key biomarkers from CC and CXC chemokine families for the accurate detection of COAD. Hub gene identification was performed using CytoHubba analysis. Clinical samples from COAD patients and normal individuals were collected and subjected to appropriate methods for DNA and RNA extraction. The expression levels of hub genes were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), while promoter methylation analysis was conducted using targeted bisulfite sequencing (bisulfite-seq). Additionally, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were utilized to validate the findings based on clinical samples. CXCL10 (C-X-C motif chemokine ligand 10), CXCL12 (C-X-C motif chemokine ligand 12), CXCL16 (C-X-C motif chemokine ligand 16), and CCL25 (CC motif chemokine ligand 25) were denoted as the key hubs among CC and CXC chemokine families. Through RT-qPCR analysis, it was found that CXCL10, CXCL12, and CXCL16 were significantly up-regulated, while CCL25 was down-regulated in COAD patients compared to healthy controls. Later on, these findings were also validated using TCGA and GEO datasets consisting of COAD and normal control samples. Furthermore, we investigated the promoter methylation status of these chemokine genes in COAD patients. Our results revealed significant dysregulation of promoter methylation, suggesting an epigenetic mechanism underlying the altered expression of CXCL10, CXCL12, CXCL16, and CCL25 in COAD. In addition to this, various additional aspects of the CCL25, CXCL10, CXCL12, and CXCL16 have also been uncovered in COAD during the present study. This study highlights the dysregulation of CXCL10, CXCL12, CXCL16, and CCL25 chemokine members in COAD patients, emphasizing their significance as potential biomarkers and therapeutic targets in the management of this deadly disease. However, further investigations are warranted to elucidate the underlying molecular mechanisms and evaluate the clinical utility of these findings.

Efficacy of surgical resection and ultra-reduced tension suture combined with superficial radiation in keloid treatment.

BACKGROUND: There are many available treatment options for keloid; however, single treatments are usually less effective. Therefore, more scientifically rational and effective combined treatment methods should be sought to solve the pain associated with keloids. AIM: To explore the efficacy and safety of surgical resection and ultra-reduced tension suture combined with superficial radiation as keloid treatment. METHODS: Fifteen keloid patients admitted to Qingdao Eighth People's Hospital from June 2020 to January 2022 were enrolled in this retrospective analysis. All patients underwent a comprehensive treatment approach comprising surgical resection, ultra-reduced tension suture incision, and superficial radiation therapy within 24 h postoperatively. The modified Vancouver Scar Scale (mVSS) and Patient and Observer Scar Assessment Scale (POSAS) were used to evaluate the treatment effect, whereas the efficacy, adverse effects, and recurrence rate were observed according to the 12-mo follow-up after treatment. RESULTS: The mVSS and POSAS scores at 1 and 6 mo after combination treatment decreased compared to before treatment (P < 0.001), and the overall response rate was 93.3%. Only one case recurred, yielding a 6.7% recurrence rate. The incidence of local chromour sedimentation rate in 1-3 mo after radiotherapy was 33.3% (5 patients), all subsiding after 6-9 mo, without complications, such as delayed wound healing or dermatitis. CONCLUSION: Surgical resection, super subtraction sutures, and superficial radiotherapy are treatment methods with short courses, low recurrence rates, and good safety profiles.

Pralsetinib-associated pneumonia in RET fusion-positive non-small cell lung cancer.

OBJECTIVE: Oncogenic alternation in RET is one of the important targets of non-small cell lung cancer (NSCLC). Pralsetinib has shown great efficacy in RET fusion-positive NSCLC, but a series of adverse reactions will inevitably occur in the meantime. We aimed to explore the clinical characteristics of patients with pneumonia and recognition it in early stage, so patients could longer benefit from pralsetinib. METHODS: This is a multicenter, retrospective study. RET fusion-positive advanced NSCLC patients who developed pneumonia during pralsetinib treatment from January 2020 to December 2022 were included. Clinical data, time to onset of pneumonia, methods of pneumonia diagnosis, treatment with pneumonia, prognosis of pneumonia, and the effect of pneumonia on the efficacy of pralsetinib. RESULTS: A total of 8 patients with pneumonia were included in the study, most of which were non-smoking female patients and the main fusion gene was KIF5B (87.5%), which was consistent with the general characteristics of RET fusion population. The median occurrence time of pralsetinib-associated pneumonia was 2.15 (range 1.1-6.63) months. All patients were infected by opportunistic pathogens, and the most common pathogen was human herpesviruses and pneumospora yerbii. Fever was always the first symptom, and timely anti-infective treatment including antibiotics, antiviral drugs, and antifungal drugs was effective. Until February 28, 2023, the median follow-up time was 18.7 months, the mean PFS of patients was 17.4 months, and the median PFS was not reached. Fortunately, patients who restarted pralsetinib after infection control continued to benefit. CONCLUSIONS: Opportunistic infection may be a unique adverse effect of pralsetinib. During the treatment of pralsetinib, we should be vigilant about the occurrence of pneumonia and achieve early recognition and timely treatment.

Ozone attenuates chemotherapy-induced peripheral neuropathy via upregulating the AMPK-SOCS3 axis.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a severe adverse reaction to chemotherapeutics, which seriously affects the outcome of chemotherapy and patients' quality of life. Although it is commonly seen, it lacks effective treatment. Our previous study found that ozone could alleviate neuropathic pain. Damage-associated molecular patterns (DAMPs) or Toll-like receptor 4 (TLR4) or tissue factor (TF)-mediated neuroinflammation and microcirculation disturbance is the main reason for CIPN. Suppressors of cytokine signaling (SOCS) 3 is an endogenous negative feedback regulator of inflammation via TLR4 inhibition. Materials and Methods: Oxaliplatin (L-OHP) was used to establish mice's CIPN model. Nociceptive responses were assessed by observing the ICR mice's incidence of foot regression in mechanical indentation response experiments. Cell signaling assays were performed by Western blotting and immunohistochemistry. The mouse leukemia cells of monocyte-macrophage line RAW 264.7 were cultured to investigate the effects of ozone administration on macrophage. Results: Ozone decreased the expression of TF in the blood and sciatic nerve. It upregulated the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-SOCS3 axis to relieve CIPN and inhibit TF expression in vivo. SOCS3 expression was induced by ozone to inhibit the p38/TF signaling in RAW 246.7 cells. Ozone also prevented L-OHP-induced sciatic nerve demyelination. Microglia activation was inhibited, and c-Fos and calcitonin gene-related peptide (CGRP) expression was decreased in the spinal dorsal horn via ozone. Conclusions: In this study, we demonstrated that ozone could alleviate CIPN by upregulating the AMPK-SOCS3 axis to inhibit TF expression, which is a potential treatment for CIPN.

A Study of Dietary Patterns Derived by Cluster Analysis and Their Association With Metabolic Dysfunction-Associated Steatotic Liver Disease Severity Among Hispanic Patients.

INTRODUCTION: Diet is a modifiable metabolic dysfunction-associated steatotic liver disease (MASLD) risk factor, but few studies have been conducted among Hispanic patients, despite the fact that MASLD prevalence and severity are highest among this ethnic subgroup. We aimed to identify prevalent dietary patterns among Hispanic patients using cluster analysis and to investigate associations with MASLD severity. METHODS: This cross-sectional analysis included 421 Harris County MASLD Cohort participants who self-reported Hispanic ethnicity and completed baseline food frequency questionnaires. All included patients had MASLD, diagnosed per standard clinical criteria. K-means analysis was used to identify clusters of patients sharing similar dietary habits. Multivariable adjusted logistic regression was used to estimate associations of dietary clusters with aminotransferases among the overall sample and with histologic steatosis, metabolic dysfunction-associated steatohepatitis, and fibrosis among a subsample of patients who underwent liver biopsy within 6 months of their baseline food frequency questionnaire (n = 186). RESULTS: We identified 2 clusters: a plant-food/prudent and a fast-food/meat pattern. The fast-food/meat pattern was associated with 2.47-fold increased odds (95% confidence interval 1.31-4.65) of more severe steatosis than the plant-food/prudent pattern after adjusting for demographics, metabolic score, physical activity, and alcohol ( q = 0.0159). No significant association was observed between diet and aminotransferases, metabolic dysfunction-associated steatohepatitis, or fibrosis. DISCUSSION: Given the importance of sociocultural influences on diet, it is important to understand dietary patterns prevalent among Hispanic patients with MASLD. Using cluster analysis, we identified 1 plant-based pattern vs 1 distinct fast-food/meat-based pattern associated with detrimental effects among our population. This information is an important starting point for tailoring dietary interventions for Hispanic patients with MASLD.

Comprehension of rectosigmoid junction cancer molecular features by comparison to the rectum or sigmoid colon cancer.

Background: Colorectal cancer (CRC) is a heterogeneous cancer. Its treatment depends on its anatomical site and molecular features. Carcinomas of the rectosigmoid junction are frequent; however, specific data on these tumors are sparse, as they are frequently assigned to either the colon or rectum. This study sought to identify the molecular features of rectosigmoid junction cancer to determine whether there should be any difference between the therapeutic management of rectosigmoid junction cancer and that of sigmoid colon or rectum cancer. Methods: The data of 96 CRC patients with carcinomas in the sigmoid colon, rectosigmoid junction, and rectum were retrospectively summarized. The next-generation sequencing (NGS) data of the patients were analyzed to study the molecular characteristics of the carcinomas in different locations of the bowel. Results: In total, there was no difference in the clinicopathologic characteristics of the three groups. TP53, APC, and KRAS genes were the top 3 alteration genes in sigmoid colon, rectosigmoid junction, and rectum cancer. The rates of the KRAS, NRAS, and PIK3CA increased as the location moved distally, while the rates of APC and BRAF decreased. Almost no significant molecular differences were found among the three groups. The prevalence of the FLT3, fms-related tyrosine kinase 1 (FLT1), and phosphoenolpyruvate carboxykinase 1 (PCK1) mutation was lower in the rectosigmoid junction group than the sigmoid colon and rectum groups (P>0.05). The proportion of the transforming growth factor beta pathway was higher in the rectosigmoid junction and rectum groups than the sigmoid colon group (39.3% vs. 34.3% vs. 18.2%, respectively, P=0.121, P=0.067, P=0.682); a higher proportion of MYC pathway was also observed in the rectosigmoid junction than that in rectum and sigmoid colon (28.6% vs. 15.2% vs. 17.1%, P=0.278, P=0.202, P=0.171). Regardless of the clustering method employed, the patients were divided into two clusters, and the composition of clusters revealed no significant differences in terms of the different locations. Conclusions: Rectosigmoid junction cancer has a distinctive molecular profile compared to the molecular profiles of the adjacent bowel segment cancers.

A novel phenotype of B cells associated with enhanced phagocytic capability and chemotactic function after ischemic stroke.

Accumulating evidence has demonstrated the involvement of B cells in neuroinflammation and neuroregeneration. However, the role of B cells in ischemic stroke remains unclear. In this study, we identified a novel phenotype of macrophage-like B cells in brain-infiltrating immune cells expressing a high level of CD45. Macrophage-like B cells characterized by co-expression of B-cell and macrophage markers, showed stronger phagocytic and chemotactic functions compared with other B cells and showed upregulated expression of phagocytosis-related genes. Gene Ontology analysis found that the expression of genes associated with phagocytosis, including phagosome- and lysosome-related genes, was upregulated in macrophage-like B cells. The phagocytic activity of macrophage-like B cells was verified by immunostaining and three-dimensional reconstruction, in which TREM2-labeled macrophage-like B cells enwrapped and internalized myelin debris after cerebral ischemia. Cell-cell interaction analysis revealed that macrophage-like B cells released multiple chemokines to recruit peripheral immune cells mainly via CCL pathways. Single-cell RNA sequencing showed that the transdifferentiation to macrophage-like B cells may be induced by specific upregulation of the transcription factor CEBP family to the myeloid lineage and/or by downregulation of the transcription factor Pax5 to the lymphoid lineage. Furthermore, this distinct B cell phenotype was detected in brain tissues from mice or patients with traumatic brain injury, Alzheimer's disease, and glioblastoma. Overall, these results provide a new perspective on the phagocytic capability and chemotactic function of B cells in the ischemic brain. These cells may serve as an immunotherapeutic target for regulating the immune response of ischemic stroke.

125I Radiotherapy combined with metronomic chemotherapy may boost the abscopal effect, leading to complete regression of liver metastasis in an SCLC patient with a 58.5-month OS: a case report.

The liver is the most common and lethal metastatic site in patients with extensive-stage small-cell lung cancer (ES-SCLC), and median survival with current standard treatment is only 9-10 months from diagnosis. Clinical observations show that a complete response (CR) is extremely rare in ES-SCLC patients with liver metastasis. Moreover, to the best of our knowledge, complete regression of liver metastasis induced by the abscopal effect, boosted primarily by permanent radioactive iodine-125 seeds implantation (PRISI), combined with a low-dose metronomic temozolomide (TMZ) regimen, has not been recorded. Here, we present the case of a 54-year-old male patient who developed multiple liver metastases from ES-SCLC after multiple lines of chemotherapy. The patient was given partial PRISI therapy (two out of six tumor lesions; 38 iodine-125 seeds in one dorsal lesion and 26 seeds in one ventral lesion), which was combined with TMZ metronomic chemotherapy (50 mg/m2/day, days 1-21, every 28 days). The abscopal effect was observed for 1 month after PRISI treatment. After about 1 year, all the liver metastases had completely disappeared, and the patient experienced no relapse. The patient eventually died of malnutrition caused by a non-tumor intestinal obstruction and had an overall survival of 58.5 months after diagnosis. PRISI combined with TMZ metronomic chemotherapy might be considered a potential therapy to trigger the abscopal effect in patients with liver metastases.

Promoting AMPK/SR-A1-mediated clearance of HMGB1 attenuates chemotherapy-induced peripheral neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect of chemotherapy with poorly understood mechanisms and few treatments. High-mobility group box 1 (HMGB1)-induced neuroinflammation is the main cause of CIPN. Here, we aimed to illustrate the role of the macrophage scavenger receptor A1 (SR-A1) in HMGB1 clearance and CIPN resolution. METHODS: Oxaliplatin (L-OHP) was used to establish a CIPN model. Recombinant HMGB1 (rHMGB1) (his tag) was used to evaluate the phagocytosis of HMGB1 by macrophages. RESULTS: In the clinic, HMGB1 expression and MMP-9 activity were increased in the plasma of patients with CIPN. Plasma HMGB1 expression was positively correlated with the cumulative dose of L-OHP and the visual analog scale. In vitro, engulfment and degradation of rHMGB1 increased and inflammatory factor expression decreased after AMP-activated protein kinase (AMPK) activation. Neutralizing antibodies, inhibitors, or knockout of SR-A1 abolished the effects of AMPK activation on rHMGB1 engulfment. In vivo, AMPK activation increased SR-A1 expression in the dorsal root ganglion, decreased plasma HMGB1 expression and MMP-9 activity, and attenuated CIPN, which was abolished by AMPK inhibition or SR-A1 knockout in the CIPN mice model. CONCLUSION: Activation of the AMPK/SR-A1 axis alleviated CIPN by increasing macrophage-mediated HMGB1 engulfment and degradation. Therefore, promoting HMGB1 clearance may be a potential treatment strategy for CIPN. Video abstract.

Neutrophil extracellular traps as a unique target in the treatment of chemotherapy-induced peripheral neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a severe dose-limiting side effect of chemotherapy and remains a huge clinical challenge. Here, we explore the role of microcirculation hypoxia induced by neutrophil extracellular traps (NETs) in the development of CIPN and look for potential treatment. METHODS: The expression of NETs in plasma and dorsal root ganglion (DRG) are examined by ELISA, IHC, IF and Western blotting. IVIS Spectrum imaging and Laser Doppler Flow Metry are applied to explore the microcirculation hypoxia induced by NETs in the development of CIPN. Stroke Homing peptide (SHp)-guided deoxyribonuclease 1 (DNase1) is used to degrade NETs. FINDINGS: The level of NETs in patients received chemotherapy increases significantly. And NETs accumulate in the DRG and limbs in CIPN mice. It leads to disturbed microcirculation and ischemic status in limbs and sciatic nerves treated with oxaliplatin (L-OHP). Furthermore, targeting NETs with DNase1 significantly reduces the chemotherapy-induced mechanical hyperalgesia. The pharmacological or genetic inhibition on myeloperoxidase (MPO) or peptidyl arginine deiminase-4 (PAD4) dramatically improves microcirculation disturbance caused by L-OHP and prevents the development of CIPN in mice. INTERPRETATION: In addition to uncovering the role of NETs as a key element in the development of CIPN, our finding provides a potential therapeutic strategy that targeted degradation of NETs by SHp-guided DNase1 could be an effective treatment for CIPN. FUNDING: This study was funded by the National Natural Science Foundation of China81870870, 81971047, 81773798, 82271252; Natural Science Foundation of Jiangsu ProvinceBK20191253; Major Project of "Science and Technology Innovation Fund" of Nanjing Medical University2017NJMUCX004; Key R&D Program (Social Development) Project of Jiangsu ProvinceBE2019732; Nanjing Special Fund for Health Science and Technology DevelopmentYKK19170.

Association of lifestyle behaviors with non-alcoholic fatty liver disease and advanced fibrosis detected by transient elastography among Hispanic/Latinos adults in the U.S.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent liver disease, with the highest prevalence observed in the U.S. among Hispanic/Latino adults. While physical activity and dietary behaviors have established protective associations with NAFLD and its severity, these associations have not been well-characterized in Hispanic/Latino adults. The purpose of this study was to assess the association of lifestyle behaviors with NAFLD and advanced fibrosis in US Hispanic/Latino adults. DESIGN: We selected all Hispanic/Latino adults from the 2017-2018 National Health and Nutrition Examination Survey (NHANES). NAFLD was defined as CAP ≥285 dB/m, and advanced fibrosis as liver stiffness measurements ≥8.6 kPa. Multivariate-adjusted logistic regression models assessed associations of physical activity and sedentary behavior (Global Physical Activity Questionnaire), as well as diet quality (Healthy Eating Index [HEI]-2015) and total energy intake (24-hour recall) with NAFLD and advanced fibrosis. RESULTS: In Hispanic/Latino adults, the overall prevalence of NAFLD was 41.5%, while the prevalence of advanced fibrosis among those with NAFLD was 17.2%. We found that higher levels of physical activity and high diet quality were associated with lower risk of NAFLD. Compared to those reporting on average 0 metabolic equivalent (MET) hours/week of physical activity, participants reporting high levels of physical activity (≥32 MET hours/week) had 40% lower risk of NAFLD (Adjusted OR = 0.60, 95%CI 0.38, 0.93). High diet quality (HEI-2015) was associated with a 30% lower risk of NAFLD (Adjusted OR = 0.70, 95% CI 0.51, 0.97) and 72% lower risk of advanced fibrosis (Adjusted OR = 0.28, 95% CI 0.12, 0.66), as compared to those with low diet quality. CONCLUSIONS: In this population-based study, high levels of physical activity and diet quality were associated with lower risk of NAFLD in Hispanic/Latino adults. Public health and medical professionals need to concentrate efforts on lifestyle behavior change in Hispanic/Latino adults who are at high risk for serious liver disease.

Coffee Intake, Caffeine Metabolism Genotype, and Survival Among Men with Prostate Cancer.

BACKGROUND: Coffee intake may lower prostate cancer risk and progression, but postdiagnosis outcomes by caffeine metabolism genotype are not well characterized. OBJECTIVE: To evaluate associations between coffee intake, caffeine metabolism genotype, and survival in a large, multicenter study of men with prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Data from The PRACTICAL Consortium database for 5727 men with prostate cancer from seven US, Australian, and European studies were included. The cases included had data available for the CYP1A2 -163C>A rs762551 single-nucleotide variant associated with caffeine metabolism, coffee intake, and >6 mo of follow-up. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable-adjusted Cox proportional hazards models across pooled patient-level data were used to compare the effect of coffee intake (categorized as low [reference], high, or none/very low) in relation to overall survival (OS) and prostate cancer-specific survival (PCSS), with stratified analyses conducted by clinical disease risk and genotype. RESULTS AND LIMITATIONS: High coffee intake appeared to be associated with longer PCSS (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.68-1.08; p = 0.18) and OS (HR 0.90, 95% CI 0.77-1.07; p = 0.24), although results were not statistically significant. In the group with clinically localized disease, high coffee intake was associated with longer PCSS (HR 0.66, 95% CI 0.44-0.98; p = 0.040), with comparable results for the group with advanced disease (HR 0.92, 95% CI 0.69-1.23; p = 0.6). High coffee intake was associated with longer PCSS among men with the CYP1A2 AA (HR 0.67, 95% CI 0.49-0.93; p = 0.017) but not the AC/CC genotype (p = 0.8); an interaction was detected (p = 0.042). No associations with OS were observed in subgroup analyses (p > 0.05). Limitations include the nominal statistical significance and residual confounding. CONCLUSIONS: Coffee intake was associated with longer PCSS among men with a CYP1A2 -163AA (*1F/*1F) genotype, a finding that will require further replication. PATIENT SUMMARY: It is likely that coffee intake is associated with longer prostate cancer-specific survival in certain groups, but more research is needed to fully understand which men may benefit and why.

Integrated investigation of the prognostic role of HLA LOH in advanced lung cancer patients with immunotherapy.

Although multiple studies have shown that loss of heterozygosity (LOH) at the human leukocyte antigen (HLA) locus is one of the mechanisms of immune escape, the effect of HLA LOH on the immunotherapy response of patients is still unclear. Based on the data of 425 Chinese lung cancer patients, the genomic characteristics with different HLA LOH statuses were analyzed. The driver genes mutation frequency, oncogenic signaling pathways mutation frequency, tumor mutational burden (TMB) and chromosomal instability (CIN) score in the HLA LOH high group was significantly higher than in the HLA LOH negative group. Transcriptome analyses revealed that pre-existing immunologically active tumor microenvironment (TME) was associated with HLA LOH negative patients. Non-small cell lung cancer (NSCLC) patients, especially for lung squamous cell carcinomas (LUSC), with HLA LOH negative have a longer survival period than those with HLA LOH. In addition, the combination of HLA LOH with TMB or programmed cell death-Ligand 1 (PD-L1) expression can further distinguish responders from non-responders. Furthermore, a comprehensive predictive model including HLA LOH status, TMB, PD-L1 expression and CD8+ T cells was constructed and exhibited a higher predictive value, which may improve clinical decision-making.

Global research landscape and trends of lung cancer immunotherapy: A bibliometric analysis.

​Background: Immunotherapy for lung cancer has been a hot research area for years. This bibliometric analysis aims to present the research trends on lung cancer immunotherapy. Method: On 1 July, 2022, the authors identified 2,941 papers on lung cancer immunotherapy by the Web of Science and extracted their general information and the total number of citations. A bibliometric analysis was carried out to present the research landscape, demonstrate the research trends, and determine the most cited papers (top papers) as well as major journals on lung cancer immunotherapy. After that, recent research hotspots were analyzed based on the latest publications in major journals. Results: These 2,941 papers were cited a total of 122,467 times. "Nivolumab vs. docetaxel in advanced non-squamous non-small-cell lung cancer" published in 2015 by Borghaei H et al. was the most cited paper (5,854 citations). Among the journals, New England Journal of Medicine was most influential. Corresponding authors represented China took part in most articles (904) and papers with corresponding authors from the USA were most cited (139.46 citations per paper). Since 2015, anti-PD-(L)1 has become the hottest research area. Conclusions: This bibliometric analysis comprehensively and quantitatively presents the research trends and hotspots based on thousands of publications, and further suggests future research directions. Moreover, the results can benefit researchers to select journals and find potential collaborators. This study can help researchers get a comprehensive impression of the research landscape, historical development, and recent hotspots in lung cancer immunotherapy and provide inspiration for further research.