Loss of fatty acid binding protein 3 ameliorates lipopolysaccharide-induced inflammation and endothelial dysfunction.

Circulating fatty acid-binding protein 3 (FABP3) is an effective biomarker of myocardial injury and peripheral artery disease (PAD). The endothelium, which forms the inner most layer of every blood vessel, is exposed to higher levels of FABP3 in PAD or following myocardial injury, but the pathophysiological role of endothelial FABP3, the effect of FABP3 exposure on endothelial cells, and related mechanisms are unknown. Here, we aimed to evaluate the pathophysiological role of endothelial FABP3 and related mechanisms in vitro. Our molecular and functional in vitro analyses show that (1) FABP3 is basally expressed in endothelial cells; (2) inflammatory stress in the form of lipopolysaccharide (LPS) upregulated endothelial FABP3 expression; (3) loss of endogenous FABP3 protected endothelial cells against LPS-induced endothelial dysfunction; however, exogenous FABP3 exposure exacerbated LPS-induced inflammation; (4) loss of endogenous FABP3 protected against LPS-induced endothelial dysfunction by promoting cell survival and anti-inflammatory and pro-angiogenic signaling pathways. Together, these findings suggest that gain-of endothelial FABP3 exacerbates, whereas loss-of endothelial FABP3 inhibits LPS-induced endothelial dysfunction by promoting cell survival and anti-inflammatory and pro-angiogenic signaling. We propose that an increased circulating FABP3 in myocardial injury or PAD patients may be detrimental to endothelial function, and therefore, therapies aimed at inhibiting FABP3 may improve endothelial function in diseased states.

Instabilities and self-organization in spatiotemporal epidemic dynamics driven by nonlinearity and noise.

Theoretical analysis of epidemic dynamics has attracted significant attention in the aftermath of the COVID-19 pandemic. In this article, we study dynamic instabilities in a spatiotemporal compartmental epidemic model represented by a stochastic system of coupled partial differential equations (SPDE). Saturation effects in infection spread-anchored in physical considerations-lead to strong nonlinearities in the SPDE. Our goal is to study the onset of dynamic, Turing-type instabilities, and the concomitant emergence of steady-state patterns under the interplay between three critical model parameters-the saturation parameter, the noise intensity, and the transmission rate. Employing a second-order perturbation analysis to investigate stability, we uncover both diffusion-driven and noise-induced instabilities and corresponding self-organized distinct patterns of infection spread in the steady state. We also analyze the effects of the saturation parameter and the transmission rate on the instabilities and the pattern formation. In summary, our results indicate that the nuanced interplay between the three parameters considered has a profound effect on the emergence of dynamical instabilities and therefore on pattern formation in the steady state. Moreover, due to the central role played by the Turing phenomenon in pattern formation in a variety of biological dynamic systems, the results are expected to have broader significance beyond epidemic dynamics.

Photocatalyzed Synthesis of a Schiff Base via C-N Bond Formation: Benzyl Alcohol as Sustainable Surrogates of Aryl Aldehydes.

The advancement of photocatalytic techniques has enabled green chemical synthesis through visible-light-mediated photochemical oxidation under mild conditions. A novel approach under visible-light conditions was facilitated by eosin-Y for the reaction between substituted benzyl alcohols and anilines, resulting in the synthesis of diverse Schiff bases. This innovative method is emphasized for its environmentally friendly nature, lack of metal catalysts, cost-effectiveness, and nontoxic characteristics.

The Effect of Concomitant Spinal Cord Injury on Postoperative Health-related Quality of Life After Traumatic Subaxial Cervical Spine Injuries: A Nationwide Registry Study.

OBJECTIVE: To evaluate the effect of spinal cord injury (SCI) on the health-related quality of life (HRQoL) in patients surgically treated for traumatic subaxial cervical spine injuries and investigate the agreement between objective neurologic outcomes and patient reported outcome measures (PROMs) in that context. STUDY DESIGN: Observational study on prospectively collected multi-institutional registry data. SETTING: Sweden. PARTICIPANTS: Patients with traumatic subaxial spine injuries identified in the Swedish Spine Registry (Swespine) between 2006 and 2016. INTERVENTIONS: Anterior, posterior, or anteroposterior cervical fixation surgery. MAIN OUTCOMES: Patient-reported outcome measures (PROMs) consisting of EQ-5D-3Lindex and Neck Disability Index (NDI). RESULTS: Among the 418 identified patients, 93 (22%) had a concomitant SCI. In this group, 30 (32%) had a complete SCI (Frankel A), and the remainder had incomplete SCIs (17%) Frankel B; 25 (27%) Frankel C; 22 (24%) Frankel D. PROMs significantly correlated with the Frankel grade (P<.001). However, post hoc analysis revealed that the differences between adjacent Frankel grades failed to reach both statistical and clinical significance. On univariable linear regression, the Frankel grade was a significant predictor of a specific index derived from the EQ-5D-3L questionnaire (EQ-5D-3Lindex) at 1, 2, and 5 years postoperatively as well as the NDI at 1 and 2 years postoperatively (P<.001). Changes of PROMs over time from 1, to 2, and 5 years postoperatively did not reach statistical significance, regardless of the presence and degree of SCI (P>.05). CONCLUSION: Overall, the Frankel grade significantly correlated with the EQ-5D-3Lindex and NDI and was a significant predictor of PROMs at 1, 2, and 5 years. PROMs were stable beyond 1 year postoperatively regardless of the severity of the SCI.

Long-term outcomes after surgery for subaxial cervical spine injuries in octogenarians, a matched population-based cohort study.

PURPOSE: We aimed to investigate surgical outcomes in octogenarians with subaxial cervical spine injuries and determine the predictors of complications and mortality. METHODS: Eligible for inclusion were all patients surgically treated between 2006 and 2018, with either anterior or posterior fixation for subaxial spine injuries. A cohort of octogenarians was identified and matched 1:1 to a corresponding cohort of younger adults. Primary outcomes were perioperative complications and mortality. RESULTS: Fifty-four patients were included in each of the octogenarian and younger groups (median age: 84.0 vs. 38.5). While the risks for surgical complications, including dural tears and wound infections, were similar between groups, the risks of postoperative medical complications, including respiratory or urinary tract infections, were significantly higher among the elderly (p < 0.05). Additionally, there were no differences in operative time (p = 0.625) or estimated blood loss (p = 0.403) between groups. The 30 and 90-day mortality rates were significantly higher among the elderly (p = 0.004 and p < 0.001). These differences were due to comorbidities in the octogenarian cohort as they were revoked when propensity score matching was performed to account for the differences in American Society of Anesthesiology (ASA) grade. Multivariable logistic regression revealed age and ASA score to be independent predictors of complications and the 90-day mortality, respectively. CONCLUSIONS: Octogenarians with comorbidities were more susceptible to postoperative complications, explaining the increased short-term mortality in this group. However, octogenarians without comorbidities had similar outcomes compared to the younger patients, indicating that overall health, including comorbidities, rather than chronological age should be considered in surgical decision-making.

Predictors of failure after primary anterior cervical discectomy and fusion for subaxial traumatic spine injuries.

INTRODUCTION: Traumatic subaxial fractures account for more than half of all cervical spine injuries. The optimal surgical approach is a matter of debate and may include anterior, posterior or a combined anteroposterior (360º) approach. Analyzing a cohort of patients initially treated with anterior cervical discectomy and fusion (ACDF) for traumatic subaxial injuries, the study aimed to identify predictors for treatment failure and the subsequent need for supplementary posterior fusion (PF). METHODS: A retrospective, single center, consecutive cohort study of all adult patients undergoing primary ACDF for traumatic subaxial cervical spine fractures between 2006 and 2018 was undertaken and 341 patients were included. Baseline clinical and radiological data for all included patients were analyzed and 11 cases of supplementary posterior fixation were identified. RESULTS: Patients were operated at a median of 2.0 days from the trauma, undergoing 1-level (78%), 2-levels (16%) and ≥ 3-levels (6.2%) ACDF. A delayed supplementary PF was performed in 11 cases, due to ACDF failure. On univariable regression analysis, older age (p = 0.017), shorter stature (p = 0.031), posterior longitudinal ligament (PLL) injury (p = 0.004), injury to ligamentum flavum (p = 0.005), bilateral facet joint dislocation (p < 0.001) and traumatic cervical spondylolisthesis (p = 0.003) predicted ACDF failure. On the multivariable regression model, older age (p = 0.015), PLL injury (p = 0.048), and bilateral facet joint dislocation (p = 0.010) remained as independent predictors of ACDF failure. CONCLUSIONS: ACDF is safe and effective for the treatment of subaxial cervical spine fractures. High age, bilateral facet joint dislocation and traumatic PLL disruption are independent predictors of failure. We suggest increased vigilance regarding these cases.

Conservative or surgical management of orbital schwannomas: a population-based case series.

INTRODUCTION: Orbital schwannomas (OS) are rare occurrences with no more than 500 cases reported in the literature. The tumor's potential to compromise the delicate neuro-ophthalmic structures within the orbit prompts surgical removal. Tumor removal is performed by ophthalmologists, often requiring a multidisciplinary surgical approach. The literature contains a very limited number of cases managed non-surgically. However, the inherent risks of orbital surgery warrant a comparison of the outcomes of conservative and surgical management strategies. AIMS: To review the national Swedish experience with the management of orbital schwannomas. METHODS: The study center is the primary Swedish referral center for the multidisciplinary management of orbital tumors, including schwannomas. During the period of 2005 to 2021, 16 patients with an OS diagnosis were managed at the center. RESULTS: Four patients initially underwent surgery where gross total resection (GTR) was achieved in three (75%) and subtotal resection (STR) in one (25%) case. The remaining 12 patients, who had a low risk of neuro-ophthalmic impairment, were managed conservatively with radiological and clinical examinations at regular intervals. After an average follow-up of 17 months, surgery was performed in three of these cases (25%). No recurrences or tumor growths were detected on radiological follow-ups (mean 50 months), and all patients experienced postoperative improvement at clinical follow-up (mean 65 months). The remainder of the conservatively treated patients (n=9) experienced no clinical progression (mean 30 months). A slight radiological tumor progression was detected in one patient after 17 months. CONCLUSION: There were no differences in long-term outcome between patients who had been managed with early surgery and those operated later after an initially conservative management. Conservatively treated patients had minimal to no symptoms and remained clinically stable throughout the follow-up period. Based on these findings, conservative management may successfully be adopted in cases with mild symptoms, no signs of compressive optic neuropathy and low risk of neuro-ophthalmic impairment. Conversion to surgical management is indicated upon clinical deterioration or tumor growth. Based on the findings of this study a decision tree for the management of orbital schwannomas is suggested.

Safety of anterior cervical corpectomy and fusion (ACCF) for the treatment of subaxial cervical spine injuries, a single center comparative matched analysis.

INTRODUCTION: Anterior Cervical Discectomy and Fusion (ACDF) and Anterior Cervical Corpectomy and Fusion (ACCF) are both common surgical procedures in the management of pathologies of the subaxial cervical spine. While recent reviews have demonstrated ACCF to provide better decompression results compared to ACDF, the procedure has been associated with increased surgical risks. Nonetheless, the use of ACCF in a traumatic context has been poorly described. The aim of this study was to assess the safety of ACCF as compared to the more commonly performed ACDF. METHODS: All patients undergoing ACCF or ACDF for subaxial cervical spine injuries spanning over 2 disc-spaces and 3 vertebral-levels, between 2006 and 2018, at the study center, were eligible for inclusion. Patients were matched based on age and preoperative ASIA score. RESULTS: After matching, 60 patients were included in the matched analysis, where 30 underwent ACDF and ACCF, respectively. Vertebral body injury was significantly more common in the ACCF group (p = 0.002), while traumatic disc rupture was more frequent in the ACDF group (p = 0.032). There were no statistically significant differences in the rates of surgical complications, including implant failure, wound infection, dysphagia, CSF leakage between the groups (p ≥ 0.05). The rates of revision surgeries (p > 0.999), mortality (p = 0.222), and long-term ASIA scores (p = 0.081) were also similar. CONCLUSION: Results of both unmatched and matched analyses indicate that ACCF has comparable outcomes and no additional risks compared to ACDF. It is thus a safe approach and should be considered for patients with extensive anterior column injury.

Dysphagia, health-related quality of life, and return to work after occipitocervical fixation.

PURPOSE: The purpose of this study was to evaluate patient-reported outcome measures (PROMS) on dysphagia, health-related quality of life (HRQoL) and return to work after occipitocervical fixation (OCF). Postoperative radiographic measurements were evaluated to identify possible predictors of dysphagia. METHODS: All individuals (≥ 18 years) who underwent an OCF at the study center or were registered in the Swedish spine registry (Swespine) between 2005 and 2019, and were still alive when the study was conducted, were eligible for inclusion. There was no overlap between the cohorts. Prospectively collected data on dysphagia (Dysphagia Short Questionnaire DSQ), HRQoL (EQ5D-3L) and return to work were used. Radiological and baseline patient data were retrospectively collected. In addition, HRQoL data of a matched sample of individuals was elicited from the Stockholm Public Health Survey 2006. RESULTS: In total, 54 individuals were included. At long-term follow-up, 26 individuals (51%) had no dysphagia, and 25 (49%) reported some degree of dysphagia: 11 (22%) had mild dysphagia, and 14 (27%) had moderate to severe dysphagia. On a group level, the OCF sample scored significantly lower EQVAS and EQ-5Dindex values compared to the general population (60.0 vs. 80.0, p = 0.016; 0.43 vs. 0.80, p < 0.001). Individuals working preoperatively returned to work after surgery. Of those responding, 88% stated that they would undergo the OCF operation if it was offered today. No predictors of dysphagia based on radiographic measurements were identified. CONCLUSION: Occipitocervical fixation results in a high frequency of long-term dysphagia. The HRQoL of OCF patients is significantly reduced compared to matched controls. However, most patients are satisfied with their surgery. No radiographic predictors of long-term dysphagia could be identified. Future prospective and systematic studies with larger samples and more objective outcome measures are needed to elucidate the causes of dysphagia in OCF.

Endothelial-to-Mesenchymal Transition in Cardiovascular Pathophysiology.

Under different pathophysiological conditions, endothelial cells lose endothelial phenotype and gain mesenchymal cell-like phenotype via a process known as endothelial-to-mesenchymal transition (EndMT). At the molecular level, endothelial cells lose the expression of endothelial cell-specific markers such as CD31/platelet-endothelial cell adhesion molecule, von Willebrand factor, and vascular-endothelial cadherin and gain the expression of mesenchymal cell markers such as α-smooth muscle actin, N-cadherin, vimentin, fibroblast specific protein-1, and collagens. EndMT is induced by numerous different pathways triggered and modulated by multiple different and often redundant mechanisms in a context-dependent manner depending on the pathophysiological status of the cell. EndMT plays an essential role in embryonic development, particularly in atrioventricular valve development; however, EndMT is also implicated in the pathogenesis of several genetically determined and acquired diseases, including malignant, cardiovascular, inflammatory, and fibrotic disorders. Among cardiovascular diseases, aberrant EndMT is reported in atherosclerosis, pulmonary hypertension, valvular disease, fibroelastosis, and cardiac fibrosis. Accordingly, understanding the mechanisms behind the cause and/or effect of EndMT to eventually target EndMT appears to be a promising strategy for treating aberrant EndMT-associated diseases. However, this approach is limited by a lack of precise functional and molecular pathways, causes and/or effects, and a lack of robust animal models and human data about EndMT in different diseases. Here, we review different mechanisms in EndMT and the role of EndMT in various cardiovascular diseases.

Protein Disulfide Isomerase 4 Is an Essential Regulator of Endothelial Function and Survival.

Endothelial autophagy plays an important role in the regulation of endothelial function. The inhibition of endothelial autophagy is associated with the reduced expression of protein disulfide isomerase 4 (PDIA-4); however, its role in endothelial cells is not known. Here, we report that endothelial cell-specific loss of PDIA-4 leads to impaired autophagic flux accompanied by loss of endothelial function and apoptosis. Endothelial cell-specific loss of PDIA-4 also induced marked changes in endothelial cell architecture, accompanied by the loss of endothelial markers and the gain of mesenchymal markers consistent with endothelial-to-mesenchymal transition (EndMT). The loss of PDIA-4 activated TGFß-signaling, and inhibition of TGFß-signaling suppressed EndMT in PDIA-4-silenced endothelial cells in vitro. Our findings help elucidate the role of PDIA-4 in endothelial autophagy and endothelial function and provide a potential target to modulate endothelial function and/or limit autophagy and EndMT in (patho-)physiological conditions.

Borane-Pyridine: An Efficient Catalyst for Direct Amidation.

Borane-pyridine acts as an efficient (5 mol%) liquid catalyst, providing improved solubility for the direct amidation of a wide range of aromatic and aliphatic carboxylic acids and amines to form secondary and tertiary carboxamides. Tolerance of potentially incompatible halo, nitro, and alkene functionalities has been demonstrated.

Identification of new modulator of DNA repairing pathways based on natural product (±)-peharmaline A.

The complex heterogenic environment of tumour mass often leads to drug resistance and facilitate chemo insensitivity triggering more malignant phenotypes among cancer patients. Major DNA-damaging cancer drugs have been consistently proven unsuccessful in terms of elevating chemo-resistance. (±)-peharmaline A, a hybrid natural product isolated from seeds of Peganum harmala L. possesses significant cytotoxic activities. Herein, we have described the design, and synthesis of a novel library of close and simplified analogues around the anticancer natural product (±)-peharmaline A and investigated their cytotoxic activities, which led to the identification of three structurally simplified lead compounds exhibiting better potency than parent natural product. Among them, demethoxy analogue of peharmaline A was further investigated for its anticancer potential eliciting demethoxy analogue as potent DNA-damage inducing agent attenuating the expression of the proteins responsible for the DNA damage repair. Therefore, this demethoxy analogue warrants detailed investigations for the confirmations of the molecular mechanism-based studies responsible for its anticancer activity. ______________________________________________________________________________.

Efficacy of Alexa, Google Assistant, and Siri for Supporting Informed Prostate Cancer Screening Decisions for African-American Men.

Prostate cancer is the most prevalent non-skin cancer among all men, but African-Americans have morbidity and mortality at significantly higher rates than White men. To reduce this burden, authorities such as the American Cancer Society recommend that men make informed/shared screening decisions with a healthcare provider. Informed/shared screening decisions require that men have adequate prostate cancer knowledge. Virtual assistants are interactive communication technologies that have become popular for seeking health information, though information quality has been mixed. No prior research has investigated the quality of prostate cancer information disseminated by virtual assistants. The purpose of this study was to determine the response rates, accuracy, breadth, and credibility of three popular virtual assistants (Alexa, Google Assistant, and Siri) for supporting informed/shared prostate cancer screening decisions for African-American men. Each virtual assistant was evaluated on a tablet, cell phone, and smart speaker using 12 frequently asked screening questions. Responses were rated dichotomously (i.e., yes/no), and analyses were conducted using SPSS. Alexa on a phone or tablet and Google Assistant on a smart speaker had the best overall performance based on a combination of response, accuracy, and credibility scores. All other assistants scored below 75% in one or more areas. Additionally, all virtual assistants lacked the breadth to support an informed/shared prostate cancer screening decision. African-American men may be especially disadvantaged by using virtual assistants for prostate cancer information because of the lack of emphasis on their greater disease risk, higher mortality rates, and appropriate ages at which they should begin screening conversations.

Titanium-Mediated Reduction of Carboxamides to Amines with Borane-Ammonia.

In this study, the successful titanium tetrachloride-catalyzed reduction of aldehydes, ketones, carboxylic acids, and nitriles with borane-ammonia was extended to the reduction (deoxygenation) of a variety of aromatic and aliphatic pri-, sec- and tert-carboxamides, by changing the stoichiometry of the catalyst and reductant. The corresponding amines were isolated in good to excellent yields, following a simple acid-base workup.

Structures and mechanism of human glycosyltransferase ß1,3-N-acetylglucosaminyltransferase 2 (B3GNT2), an important player in immune homeostasis.

ß1,3-N-acetylglucosaminyltransferases (B3GNTs) are Golgi-resident glycosyltransferases involved in the biosynthesis of poly-N-acetyl-lactosamine chains. They catalyze the addition of the N-acetylglucosamine to the N-acetyl-lactosamine repeat as a key step of the chain elongation process. Poly-N-acetyl-lactosamine is involved in the immune system in many ways. Particularly, its long chain has been demonstrated to suppress excessive immune responses. Among the characterized B3GNTs, B3GNT2 is the major poly-N-acetyl-lactosamine synthase, and deletion of its coding gene dramatically reduced the cell surface poly-N-acetyl-lactosamine and led to hypersensitive and hyperresponsive immunocytes. Despite the extensive functional studies, no structural information is available to understand the molecular mechanism of B3GNT2, as well as other B3GNTs. Here we present the structural and kinetic studies of the human B3GNT2. Five crystal structures of B3GNT2 have been determined in the unliganded, donor substrate-bound, acceptor substrate-bound, and product(s)-bound states at resolutions ranging from 1.85 to 2.35 Å. Kinetic study shows that the transglycosylation reaction follows a sequential mechanism. Critical residues involved in recognition of both donor and acceptor substrates as well as catalysis are identified. Mutations of these invariant residues impair B3GNT2 activity in cell assays. Structural comparison with other glycosyltransferases such as mouse Fringe reveals a novel N-terminal helical domain of B3GNTs that may stabilize the catalytic domain and distinguish among different acceptor substrates.

Coelacanth SERINC2 Inhibits HIV-1 Infectivity and Is Counteracted by Envelope Glycoprotein from Foamy Virus.

SERINC5 restricts nef-defective HIV-1 by affecting early steps of the virus life cycle. Distantly related retroviruses with a wide host range encode virulent factors in response to challenge by SERINC5. However, the evolutionary origins of this antiretroviral activity, its prevalence among the paralogs, and its ability to target retroviruses remain understudied. In agreement with previous studies, we found that four human SERINC paralogs inhibit nef-defective HIV-1, with SERINC2 being an exception. Here, we demonstrate that this lack of activity in human SERINC2 is associated with its post-whole-genome duplication (post-WGD) divergence, as evidenced by the ability of pre-WGD orthologs from Saccharomyces cerevisiae and flies and a post-WGD-proximate SERINC2 from coelacanths to inhibit the virus. Intriguingly, Nef is unable to counter coelacanth SERINC2, indicating that such activity was directed toward other retroviruses found in coelacanths (like foamy viruses). However, foamy virus-derived vectors are intrinsically resistant to the action of SERINC2, and we show that the foamy virus envelope confers this resistance by affecting its steady-state levels. Our study highlights an ancient origin of antiretroviral activity in SERINCs and a hitherto-unknown interaction with a foamy virus. IMPORTANCESERINC5 constitutes a critical barrier to the propagation of retroviruses, as highlighted by parallel emergence of anti-SERINC5 activities among distant retroviral lineages. Therefore, understanding the origin and evolution of these host factors will provide key information about virus-host relationships that can be exploited for future drug development. Here, we show that SERINC5-mediated nef-defective HIV-1 infection inhibition is evolutionarily conserved. SERINC2 from coelacanth restricts HIV-1, and it was functionally adapted to target foamy viruses. Our findings provide insights into the evolutionary origin of antiretroviral activity in the SERINC gene family and uncover the role of SERINCs in shaping the long-term conflicts between retroviruses and their hosts.

Ready Access to Densely Substituted Furans Using Tsuji-Wacker-Type Cyclization.

A competent method for the construction of highly substituted furans catalyzed by Pd(II) and Cu(II) chloride has been developed. The method provides easy access to di-, tri-, and tetrasubstituted furans from corresponding diols with relatively mild conditions in a unified strategy. The developed method has been successfully tested with more than 25 substrates, which resulted in furans of multiple substitution patterns with up to 84% isolated yields.

Development of minimal physiologically-based pharmacokinetic-pharmacodynamic models for characterizing cellular kinetics of CAR T cells following local deliveries in mice.

Chimeric antigen receptor (CAR) T cell therapies have revolutionized the treatment of hematologic malignancies and have potentials for solid tumor treatment. To overcome limited CAR T cell infiltration to solid tumors, local delivery of CAR T cells is a practical strategy that has shown promising therapeutic outcome and safety profile in the clinic. It is of great interest to understand the impact of dosing routes on CAR T cell distribution, subsequent proliferation and tumor killing in a quantitative manner to identify key factors that contribute to CAR T efficacy and safety. In this study, we established mouse minimal physiologically-based pharmacokinetic (mPBPK) models combined with pharmacodynamic (PD) components to delineate CAR T cell distribution, proliferation, tumor growth, and tumor cell killing in the cases of pleural and liver tumors. The pleural tumor model reasonably captured published CAR T cellular kinetic and tumor growth profiles in mice. The mPBPK-PD simulation of a liver tumor mouse model showed a substantial increase in initial tumor infiltration and earlier CAR T cell proliferation with local hepatic artery delivery compared to portal vein and intravenous (i.v.) injections whereas portal vein injection showed little difference from i.v. administration, suggesting the importance of having the injection site close to tumor for maximal effect of non-systemic administration. Blood flow rate in the liver tumor was found to be a sensitive parameter for cellular kinetics and efficacy, indicating a potential role of tumor vascularization in the efficacy of CAR T cell therapies.

Trimethyl Borate-Catalyzed, Solvent-Free Reductive Amination.

Solvent-free reductive amination of aldehydes and ketones with aliphatic and aromatic amines in high-to-excellent yields has been achieved with sub-stoichiometric trimethyl borate as promoter and ammonia borane as reductant.