tbuckley/cabot-search huggingface dataset:
Injectable Asymmetric Adhesive‐Antifouling Bifunctional Hydrogel for Peritoneal Adhesion Prevention
Authors: Zhongming Zhao, Hong Sun, Chaojie Yu, Baijun Liu, Rui Liu, Qi Yang, Bingyan Guo, Xiuqiang Li, Mengmeng Yao, Fanglian Yao, Hong Zhang, Junjie Li
Journal: Advanced Healthcare Materials (2023)

Abstract Peritoneal adhesion is a common problem after abdominal surgery and can lead to various medical problems. In response to the lack of in situ retention and pro‐wound healing properties of existing anti‐adhesion barriers, this work reports an injectable adhesive‐antifouling bifunctional hydrogel (AAB‐hydrogel). This AAB‐hydrogel can be constructed by “two‐step” injection. The tissue adhesive hydrogel based on gallic acid‐modified chitosan and aldehyde‐modified dextran is prepared as the bottom hydrogel (B‐hydrogel) by Schiff base reaction. The aldehyde‐modified zwitterionic dextran/carboxymethyl chitosan‐based hydrogel is formed on the B‐hydrogel surface as the antifouling top hydrogel (T‐hydrogel). The AAB‐hydrogel exhibits good bilayer binding and asymmetric properties, including tissue adhesive, antifouling, and antimicrobial properties. To evaluate the anti‐adhesion effect in vivo, the prepared hydrogels are injected onto the wound surface of a mouse abdominal wall abrasion‐cecum defect model. Results suggest that the AAB‐hydrogel has antioxidant capacity and can reduce the postoperative inflammatory response by modulating the macrophage phenotype. Moreover, the AAB‐hydrogel could effectively inhibit the formation of postoperative adhesions by reducing protein deposition, and resisting fibroblast adhesions and bacteria attacking. Therefore, AAB‐hydrogel is a promising candidate for the prevention of postoperative peritoneal adhesions.
The RNA m6A demethylase ALKBH5 drives emergency granulopoiesis and neutrophil mobilization by upregulating G-CSFR expression
Authors: Yang Liu, Renjie Song, Zhike Lu, Lu Zhao, Xinyi Zhan, Yini Li, Xuetao Cao
Journal: Cellular and Molecular Immunology (2023)

Abstract Emergency granulopoiesis and neutrophil mobilization that can be triggered by granulocyte colony-stimulating factor (G-CSF) through its receptor G-CSFR are essential for antibacterial innate defense. However, the epigenetic modifiers crucial for intrinsically regulating G-CSFR expression and the antibacterial response of neutrophils remain largely unclear. N 6 -methyladenosine (m 6 A) RNA modification and the related demethylase alkB homolog 5 (ALKBH5) are key epigenetic regulators of immunity and inflammation, but their roles in neutrophil production and mobilization are still unknown. We used cecal ligation and puncture (CLP)-induced polymicrobial sepsis to model systemic bacterial infection, and we report that ALKBH5 is required for emergency granulopoiesis and neutrophil mobilization. ALKBH5 depletion significantly impaired the production of immature neutrophils in the bone marrow of septic mice. In addition, Alkbh5 -deficient septic mice exhibited higher retention of mature neutrophils in the bone marrow and defective neutrophil release into the circulation, which led to fewer neutrophils at the infection site than in their wild-type littermates. During bacterial infection, ALKBH5 imprinted production- and mobilization-promoting transcriptome signatures in both mouse and human neutrophils. Mechanistically, ALKBH5 erased m 6 A methylation on the CSF3R mRNA to increase the mRNA stability and protein expression of G-CSFR, consequently upregulating cell surface G-CSFR expression and downstream STAT3 signaling in neutrophils. The RIP-qPCR results confirmed the direct binding of ALKBH5 to the CSF3R mRNA, and the binding strength declined upon bacterial infection, accounting for the decrease in G-CSFR expression on bacteria-infected neutrophils. Considering these results collectively, we define a new role of ALKBH5 in intrinsically driving neutrophil production and mobilization through m 6 A demethylation-dependent posttranscriptional regulation, indicating that m 6 A RNA modification in neutrophils is a potential target for treating bacterial infections and neutropenia.
Elevated FBXL6 activates both wild-type KRAS and mutant KRASG12D and drives HCC tumorigenesis via the ERK/mTOR/PRELID2/ROS axis in mice
Authors: Hao-Jun Xiong, Hong-Qiang Yu, Jie Zhang, Lei Fang, Di Wu, Xiao-Tong Lin, Chuan-Ming Xie
Journal: Military Medical Research (2023)

Abstract Background Kirsten rat sarcoma (KRAS) and mutant KRAS G12D have been implicated in human cancers, but it remains unclear whether their activation requires ubiquitination. This study aimed to investigate whether and how F-box and leucine-rich repeat 6 (FBXL6) regulates KRAS and KRAS G12D activity in hepatocellular carcinoma (HCC). Methods We constructed transgenic mouse strains LC ( LSL-Fbxl6 KI/ + ;Alb-Cre , n = 13), KC ( LSL-Kras G12D/ + ;Alb-Cre , n = 10) and KLC ( LSL-Kras G12D/ + ;LSL-Fbxl6 KI/ + ;Alb-Cre , n = 12) mice, and then monitored HCC for 320 d. Multiomics approaches and pharmacological inhibitors were used to determine oncogenic signaling in the context of elevated FBXL6 and KRAS activation. Co‑immunoprecipitation (Co-IP), Western blotting, ubiquitination assay and RAS activity detection assay were employed to investigate the underlying molecular mechanism by which FBXL6 activates KRAS. The pathological relevance of the FBXL6/KRAS/extracellular signal-regulated kinase (ERK)/mammalian target of rapamycin (mTOR)/proteins of relevant evolutionary and lymphoid interest domain 2 (PRELID2) axis was evaluated in 129 paired samples from HCC patients. Results FBXL6 is highly expressed in HCC as well as other human cancers ( P &lt; 0.001). Interestingly, FBXL6 drives HCC in transgenic mice. Mechanistically, elevated FBXL6 promotes the polyubiquitination of both wild-type KRAS and KRAS G12D at lysine 128, leading to the activation of both KRAS and KRAS G12D and promoting their binding to the serine/threonine-protein kinase RAF, which is followed by the activation of mitogen-activated protein kinase kinase (MEK)/ERK/mTOR signaling. The oncogenic activity of the MEK/ERK/mTOR axis relies on PRELID2, which induces reactive oxygen species (ROS) generation. Furthermore, hepatic FBXL6 upregulation facilitates KRAS G12D to induce more severe hepatocarcinogenesis and lung metastasis via the MEK/ERK/mTOR/PRELID2/ROS axis. Dual inhibition of MEK and mTOR effectively suppresses tumor growth and metastasis in this subtype of cancer in vivo. In clinical samples, FBXL6 expression positively correlates with p-ERK ( χ 2 = 85.067, P &lt; 0.001), p-mTOR ( χ 2 = 66.919, P &lt; 0.001) and PRELID2 ( χ 2 = 20.891, P &lt; 0.001). The Kaplan–Meier survival analyses suggested that HCC patients with high FBXL6/p-ERK levels predicted worse overall survival (log‑rank P &lt; 0.001). Conclusions FBXL6 activates KRAS or KRAS G12D via ubiquitination at the site K128, leading to activation of the ERK/mTOR/PRELID2/ROS axis and tumorigenesis. Dual inhibition of MEK and mTOR effectively protects against FBXL6- and KRAS G12D -induced tumorigenesis, providing a potential therapeutic strategy to treat this aggressive subtype of liver cancer.
Characterization changes and research waste in randomized controlled trials of global bariatric surgery over the past 20 years:cross-sectional study
Authors: Ze-ning Huang, Wen-Wu Qiu, Qi-Chen He, Zhi-quan Zhang, Binbin Xu, Chang-yue Zheng, Chao-Hui Zheng, Jian Wei Xie, Jia-Bin Wang, Jian-Xian Lin, Qi-yue Chen, Long-Long Cao, Chang-ming Huang, Jun Lu, Ping Li
Journal: International Journal of Surgery (2023)

The results of several large randomized controlled trials (RCTs) have changed the clinical practice of bariatric surgery. However, the characteristics of global RCTs of bariatric surgery have not been reported internationally and whether there was research waste in these RCTs is unknown.
Notch signaling in thyrocytes is essential for adult thyroid function and mammalian homeostasis
Authors: Lluc Mosteiro, Thi Thu Thao Nguyen, Simona Hankeova, Daniel Alvarez-Sierra, Mike Reichelt, Shannon M. Vandriel, Zijuan Lai, Feroza K. Choudhury, Dewakar Sangaraju, Binita M. Kamath, Alexis Scherl, Ricardo Pujol-Borrell, Robert Piskol, Christian W. Siebel
Journal: Nature Metabolism (2023)
A commentary on ‘approaches of laparoscopic anatomical liver resection of segment 8 for hepatocellular carcinoma: a retrospective cohort study of short-term results at multiple centers in China’
Authors: Qingyun Xie, Fengwei Gao
Journal: International Journal of Surgery (2023)

aDepartment of Hepato-Pancreato-biliary Surgery,People's Hospital of Leshan, Leshan, 614000, China bLiver Transplantation Center, State Key Laboratory of Biotherapy and Cancer, Center, West China Hospital, Sichuan University and Collaborative Innovation Center, of Biotherapy, Chengdu, 610041, China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Liver Transplantation Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, No. 37, Guoxue Lane, Wuhou District, Chengdu, Sichuan Province, China, Tel: +86 18990609527. E-mail address: [email protected] (F. Gao). This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-sa/4.0/
A commentary on “Does the time interval between sentinel lymph node biopsy and completion lymph node dissection affect outcome in malignant melanoma? A retrospective cohort study” – correspondence
Authors: Muthupandian Saravanan, Jesu Arockiaraj, Melaku A. Belete
Journal: International Journal of Surgery (2023)

Saravanan, Muthupandian PhD; Arockiaraj, Jesu PhD; Belete, Melaku Ashagrie Author Information
Pulmonary vagus nerve transection for chronic cough after video-assisted lobectomy: a randomized controlled trial
Authors: Qianqian Zhang, Yong Ge, Teng Sun, Shoujie Feng, Cheng Zhang, Tao Hong, Xinlong Liu, Yuan Han, Jun-Li Cao, Hao Zhang
Journal: International Journal of Surgery (2023)

Background: Chronic cough is common after lobectomy. Vagus nerves are part of the cough reflex. Accordingly, transection of the pulmonary branches of vagus nerve may prevent chronic cough. And there are no clear recommendations on the management of the pulmonary branches of vagus in any thoracic surgery guidelines. Methods: This is a single-center, randomized controlled trial. Adult patients undergoing elective video-assisted thoracoscopic lobectomy and lymphadenectomy were randomized at a 1:1 ratio to undergo a sham procedure (control group) or transection of the pulmonary branches of the vagus nerve that innervate the bronchial stump plus the caudal-most large pulmonary branch of the vagus nerve. The primary outcome was the rate of chronic cough, as assessed at 3 months after surgery in the intent-to-treat population. Results: Between 1 February 2020 and 1 August 2020, 116 patients (59.6±10.1 years of age; 45 men) were randomized (58 in each group). All patients received designated intervention. The rate of chronic cough at 3 months was 19.0% (11/58) in the vagotomy group versus 41.4% (24/58) in the control group (OR=0.332, 95% CI: 0.143–0.767; P =0.009). In the 108 patients with 2-year assessment, the rate of persistent cough was 12.7% (7/55) in the control and 1.9% (1/53) in the vagotomy group ( P =0.032). The two groups did not differ in postoperative complications and key measures of pulmonary function, for example, maximal voluntary ventilation, diffusing capacity of the lungs for carbon monoxide, and forced expiratory volume. Conclusion: Transecting the pulmonary branches of vagus nerve that innervate the bronchial stump plus the caudal-most large pulmonary branch decreased the rate of chronic cough without affecting pulmonary function in patients undergoing video-assisted lobectomy and lymphadenectomy.
Clinical efficacy and biomarker analysis of neoadjuvant camrelizumab plus chemotherapy for early-stage triple-negative breast cancer: a experimental single-arm phase II clinical trial pilot study
Authors: Chunhui Zheng, Yanbing Liu, Xue’er Wang, Zhao Bi, Pengfei Qiu, Guangdong Qiao, Xiang Bi, Zhiqiang Shi, Zhaopeng Zhang, Peng Chen, Xiao Sun, Chunjian Wang, Shiguang Zhu, Xiangjing Meng, Yunjie Song, Yingxue Qi, Lu Li, Ningning Luo, Yongsheng Wang
Journal: International Journal of Surgery (2023)

Background: Triple-negative breast cancer (TNBC) is associated with a dismal prognosis. Immune checkpoint inhibitors have shown promising antitumor activity in neoadjuvant settings. This single-arm, phase II trial aimed to evaluate the efficacy and safety of camrelizumab plus chemotherapy as the neoadjuvant therapy (NAT) in early TNBC. Methods: Patients received eight cycles of camrelizumab plus nonplatinum-based chemotherapy. The primary endpoint was total pathological complete response (pCR). Secondary endpoints included the breast pathological complete response (bpCR), adverse events (AEs). Multiomics biomarkers were assessed as exploratory objective. Results: Twenty of 23 TNBC patients receiving NAT underwent surgery, with the total pCR rate of 65% (13/20) and bpCR rate of 70% (14/20). Grade ≥3 treatment-related AEs were observed in 14 (60.9%) patients, with the most common AE being neutropenia (65.2%). Tumor immune microenvironment was analyzed between pCR and non-pCR samples before and after the NAT. Gene expression profiling showed a higher immune infiltration in pCR patients than non-pCR patients in pre-NAT samples. Through establishment of a predictive model for the NAT efficacy, TAP1 and IRF4 were identified as the potential predictive biomarkers for response to the NAT. Gene set enrichment analysis revealed the glycolysis and hypoxia pathways were significantly activated in non-pCR patients before the NAT, and this hypoxia was aggravated after the NAT. Conclusion: Camrelizumab plus nonplatinum-based chemotherapy shows a promising pCR rate in early-stage TNBC, with an acceptable safety profile. TAP1 and IRF4 may serve as potential predictive biomarkers for response to the NAT. Aggravated hypoxia and activated glycolysis after the NAT may be associated with the treatment resistance.
Light‐Enhanced Hypoxia‐Responsive Gene Editing for Hypoxia‐Resistant Photodynamic and Immunotherapy
Authors: Suchen Qu, Yu Ji, Liansheng Fan, Tao Yan, Gaoshuang Zhu, Hongxiu Song, Kaiyong Yang, Xin Han
Journal: Advanced Healthcare Materials (2023)

Hypoxia is a key hallmark of solid tumors and can cause resistance to various treatments such as photodynamics and immunotherapy. Microenvironment-responsive gene editing provides a powerful tool to overcome hypoxia resistance and remodel hypoxic microenvironments for enhanced tumor therapy. Here, a light-enhanced hypoxia-responsive multifunctional nanocarrier is developed to perform spatiotemporal specific dual gene editing for enhanced photodynamic and immunotherapy in breast cancer. As a gated molecule of nanocarrier, the degradation of azobenzene moieties under hypoxic conditions triggers controllable release of Cas9 ribonucleoprotein in hypoxic site of the tumor. Hyaluronic acid is conjugated with chloramine e6 to coat mesoporous silica nanoparticles for targeted delivery in tumors and generation of high levels of reactive oxygen species, which can result in increased hypoxia levels for effective cleavage of azobenzene bonds to improve gene editing efficiency and reduce toxic side effects with light irradiation. Moreover, dual targeting HIF-1α and PD-L1 in the anoxic microenvironments can overcome hypoxia resistance and remodel immune microenvironments, which reduces tumor plasticity and resistance to photodynamic and immunotherapy. In summary, a light-enhanced hypoxia responsive nanocomposite is developed for controllable gene editing which holds great promise for synergistic hypoxia-resistant photodynamic and immunotherapy.
Chemical genetic control of cytokine signaling in CAR-T cells using lenalidomide-controlled membrane-bound degradable IL-7
Authors: Michael C. Kann, Emily M. Schneider, Antonio J. Almazan, Isabel C. Lane, Amanda A. Bouffard, Valentina M. Supper, Hana N. Takei, Alexander Tepper, Mark B. Leick, Rebecca C. Larson, Benjamin L. Ebert, Marcela V. Maus, Max Jan
Journal: Leukemia (2023)
Combining Multifunctional Delivery System with Blood–Brain Barrier Reversible Opening Strategy for the Enhanced Treatment of Alzheimer's Disease
Authors: Jia Ke, Caini Yu, Sufen Li, Yiling Hong, Yichong Xu, Kai Wang, Tingting Meng, Yuan Ping, Qiang Fu, Hong Yuan, Fuqiang Hu
Journal: Advanced Healthcare Materials (2023)

Abstract Alzheimer's disease (AD) is a neurodegenerative illness characterized by intracellular tau‐phosphorylation, β‐amyloid (Aβ) plaques accumulation, neuroinflammation, and impaired behavioral ability. Owing to the lack of effective brain delivery approaches and the presence of the blood–brain barrier (BBB), current AD therapeutic endeavors are severely limited. Herein, a multifunctional delivery system (RVG‐DDQ/PDP@siBACE1) is elaborately combined with a protein kinase B (AKT) agonist (SC79) for facilitating RVG‐DDQ/PDP@siBACE1 to target and penetrate BBB, enter brain parenchyma, and further accumulate in AD brain lesion. Moreover, compared with the unitary dose of RVG‐DDQ/PDP@siBACE1, this collaborative therapy strategy exhibits a distinctive synergistic function including scavenging reactive oxygen species (ROS), decreasing of Aβ production, alleviating neuroinflammation by promoting the polarized microglia into the anti‐inflammatory M2‐like phenotype and significantly enhancing the cognitive functions of AD mice. More strikingly, according to these results, an innovative signaling pathway “lncRNA MALAT1/miR‐181c/BCL2L11” is found that can mediate the neuronal apoptosis of AD. Taken together, combining the brain targeted delivery system with noninvasive BBB opening can provide a promising strategy and platform for targeting treatment of AD and other neurodegenerative diseases.
DON of Hope: Starving Pancreatic Cancer by Glutamine Antagonism
Authors: Ray Pillai, Thales Papagiannakopoulous
Journal: Cancer Research (2023)

Abstract A promising approach to treat solid tumors involves disrupting their reliance on glutamine, a key component for various metabolic processes. Traditional attempts using glutamine inhibitors like 6-diazo-5-oxo-L-norleucine (DON) and CB-839 were unsuccessful, but new hope arises with DRP-104, a prodrug of DON. This compound effectively targets tumor metabolism while minimizing side effects. In a recent study published in Nature Cancer, Encarnación-Rosado and colleagues demonstrated in preclinical models that pancreatic ductal adenocarcinoma (PDAC) responds well to DRP-104, although tumors adapt through the MEK/ERK signaling pathway, which can be countered by the MEK inhibitor trametinib. In a related study, Recouvreux and colleagues found that DON is effective against pancreatic tumors, revealing that PDAC tumors upregulate asparagine synthesis in response to DON, making them susceptible to asparaginase treatment. Both studies underscore the potential of inhibiting glutamine metabolism and adaptive pathways as a promising strategy against PDAC. These findings pave the way for upcoming clinical trials utilizing DRP-104 and similar glutamine antagonists in the battle against solid tumors.
Development of respiratory care guidelines for Duchenne muscular dystrophy in the UK: key recommendations for clinical practice
Authors: Anne-Marie Childs, Catherine Turner, Ronan Astin, Stephen Bianchi, John Bourke, Vicki Cunningham, Lisa Edel, Christopher Edwards, Phillippa Farrant, Jane Heraghty, Meredith James, Charlotte Massey, Ben Messer, Jassi Michel Sodhi, Patrick Brian Murphy, Marianela Schiava, Ajit Thomas, Federica Trucco, Michela Guglieri
Journal: Thorax (2023)

Significant inconsistencies in respiratory care provision for Duchenne muscular dystrophy (DMD) are reported across different specialist neuromuscular centres in the UK. The absence of robust clinical evidence and expert consensus is a barrier to the implementation of care recommendations in public healthcare systems as is the need to increase awareness of key aspects of care for those living with DMD. Here, we provide evidenced-based and/or consensus-based best practice for the respiratory care of children and adults living with DMD in the UK, both as part of routine care and in an emergency. Methodology Initiated by an expert working group of UK-based respiratory physicians (including British Thoracic Society (BTS) representatives), neuromuscular clinicians, physiotherapist and patient representatives, draft guidelines were created based on published evidence, current practice and expert opinion. After wider consultation with UK respiratory teams and neuromuscular services, consensus was achieved on these best practice recommendations for respiratory care in DMD. Result The resulting recommendations are presented in the form of a flow chart for assessment and monitoring, with additional guidance and a separate chart setting out key considerations for emergency management. The recommendations have been endorsed by the BTS. Conclusions These guidelines provide practical, reasoned recommendations for all those managing day-to-day and acute respiratory care in children and adults with DMD. The hope is that this will support patients and healthcare professionals in accessing high standards of care across the UK.
Precocious infant fecal microbiome promotes enterocyte barrier dysfuction, altered neuroendocrine signaling and associates with increased childhood obesity risk
Authors: Germaine J. M. Yong, Cara E. Porsche, Alexandra R. Sitarik, Kei E. Fujimura, Kathryn McCauley, Dat T. Nguyen, Albert M. Levin, Kimberley J. Woodcroft, Dennis R. Ownby, Andrew G. Rundle, Christine C. Johnson, Andrea Cassidy-Bushrow, Susan V. Lynch
Journal: Gut Microbes (2023)

Early life gut microbiome composition has been correlated with childhood obesity, though microbial functional contributions to disease origins remain unclear. Here, using an infant birth cohort (n = 349) we identify a distinct fecal microbiota composition in 1-month-old infants with the lowest rate of exclusive breastfeeding, that relates with higher relative risk for obesity and overweight phenotypes at two years. Higher-risk infant fecal microbiomes exhibited accelerated taxonomic and functional maturation and broad-ranging metabolic reprogramming, including reduced concentrations of neuro-endocrine signals. In vitro, exposure of enterocytes to fecal extracts from higher-risk infants led to upregulation of genes associated with obesity and with expansion of nutrient sensing enteroendocrine progenitor cells. Fecal extracts from higher-risk infants also promoted enterocyte barrier dysfunction. These data implicate dysregulation of infant microbiome functional development, and more specifically promotion of enteroendocrine signaling and epithelial barrier impairment in the early-life developmental origins of childhood obesity.
Gazing into the Proteomic Crystal Ball: Predicting Survival in Idiopathic Pulmonary Fibrosis
Authors: Joyce S. Lee, Toby M. Maher
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Gazing into the Proteomic Crystal Ball: Predicting Survival in Idiopathic Pulmonary Fibrosis." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.