Rhodium-Catalyzed Asymmetric Transfer Hydrogenation of Aryl Ketones Involving Free Phenolic Hydroxyl Group(s).

A straightforward asymmetric transfer hydrogenation for accessing enantiomerically enriched secondary benzyl alcohols involving free phenolic hydroxyl group(s) under mild conditions was developed. Various of optical pure aryl alcohols with a remarkable functional group compatibility were achieved with 78%-97% yields, 84%->99% ee's and up to 10 000 TON. This rhodium-catalyzed reaction could be performed in a gram-scale without loss of the efficiency. Furthermore, the synthetic utility has also been demonstrated in the asymmetric synthesis of (S)-adrenaline and (S)-phenylephrine.

Changes in serum sodium concentration during hemodialysis is a predictor of mortality and cardio-cerebrovascular event.

BACKGROUND: Previous study consistently showed that lower serum sodium (SNa) was associated with a greater risk of mortality in hemodialysis (HD) patients. However, few studies have focused on the change in SNa (ΔSNa = post-HD SNa - pre-HD SNa) during an HD session. METHODS: In a retrospective cohort of maintenance HD adults, all-cause mortality and cardio-cerebrovascular event (CCVE) were followed up for a medium of 82 months. Baseline pre-HD SNa and ΔSNa were collected; time-averaged pre-HD SNa and ΔSNa were computed as the mean values within 1-year, 2-year and 3-year intervals after enrollment. Cox proportional hazards models were used to evaluate the relationships of pre-HD and ΔSNa with outcomes. RESULTS: Time-averaged pre-HD SNa were associated with all-cause mortality (2-year pre-HD SNa: HR [95% CI] 0.86 [0.74-0.99], p = 0.042) and CCVE (3-year pre-HD SNa: HR [95% CI] 0.83 [0.72-0.96], p = 0.012) with full adjustment. Time-averaged ΔSNa also demonstrated an association with all-cause mortality (3-year ΔSNa: HR [95% CI] 1.26 [1.03-1.55], p = 0.026) as well as with CCVE (3-year ΔSNa: HR [95% CI] 1.51 [1.21-1.88], p = <0.001) when fully adjusted. Baseline pre-HD SNa and ΔSNa didn't exhibit association with both outcomes. CONCLUSIONS: Lower time-averaged pre-HD SNa and higher time-averaged ΔSNa were associated with a greater risk of all-cause mortality and CCVE in HD patients.

Intra-dialytic blood pressure variability is a greater predictor of cardiovascular events in hemodialysis patients.

BACKGROUND: Short-term and long-term blood pressure variability (BPV) in hemodialysis (HD) population are risk factors of cardiovascular diseases (CVD) and all-cause mortality. There is no full consensus on the best BPV metric. We compared the prognostic role of intra-dialytic and visit-to-visit BPV metrics for CVD morbidity and all-cause mortality in HD patients. METHODS: A retrospective cohort of 120 patients on HD was followed up for 44 months. Systolic blood pressure (SBP) and baseline characteristics were collected for 3 months. We calculated intra-dialytic and visit-to-visit BPV metrics, including standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM), average real variability (ARV) and residual. The primary outcomes were CVD events and all-cause mortality. RESULTS: In Cox regression analysis, both intra-dialytic and visit-to-visit BPV metrics were associated with increased CVD events (intra-dialytic CV: HR 1.70, 95% CI 1.28-2.27, p < 0.01; visit-to-visit CV: HR 1.55, 95% CI 1.12-2.16, p < 0.01), but not associated with increased all-cause mortality (intra-dialytic CV: HR 1.32, 95% CI 0.99-1.76, p = 0.06; visit-to-visit CV: HR 1.22, 95% CI 0.91-1.63, p = 0.18). Overall, intra-dialytic BPV showed greater prognostic ability than visit-to-visit BPV for both CVD event (AUC of intra-dialytic BPV and visit-to-visit BPV metrics respectively: SD 0.686, 0.606; CV 0.672, 0.425; VIM 0.677, 0.581; ARV 0.684, 0.618; residual 0.652, 0.586) and all-cause mortality (SD 0.671, 0.608; CV 0.662, 0.575; VIM 0.669, 0.581; ARV 0.529, 0.588; residual 0.651, 0.602). CONCLUSION: Compared to visit-to-visit BPV, intra-dialytic BPV is a greater predictor of CVD event in HD patients. No obvious priority was found among various BPV metrics.

Efficient Adsorption of Acetylene over CO2 in Bioinspired Covalent Organic Frameworks.

Rational design of covalent organic frameworks (COFs) to broaden their diversity is highly desirable but challenging due to the limited, expensive, and complex building blocks, especially compared with other easily available porous materials. In this work, we fabricated two novel bioinspired COFs, namely, NUS-71 and NUS-72, using reticular chemistry with ellagic acid and triboronic acid-based building blocks. Both COFs with AB stacking mode exhibit high acetylene (C2H2) adsorption capacity and excellent separation performance for C2H2/CO2 mixtures, which is significant but rarely explored using COFs. The impressive affinities for C2H2 appear to be related to the sandwich structure formed by C2H2 and the host framework via multiple host-guest interactions. This work not only represents a new avenue for the construction of low-cost COFs but also expands the variety of the COF family using natural biochemicals as building blocks for broad application.

Asymmetric transfer hydrogenation of cycloalkyl vinyl ketones to allylic alcohols catalyzed by ruthenium amido complexes.

A chemoselective 1,2-reduction of cycloalkyl vinyl ketones via asymmetric transfer hydrogenation is described. The reduction proceeded smoothly with a chiral diamine ruthenium complex as a catalyst and a HCOOH-NEt3 azeotrope as both a hydrogen source and solvent under mild conditions. A wide range of 1-cycloalkyl chiral allylic alcohols were obtained in good yields and up to 87% ee. It was found that the alkyl group plays an important role in the enantioselectivity.

Discovery of novel oxoindolin derivatives as atypical dual inhibitors for DNA Gyrase and FabH.

The antibacterial agents and therapies today are facing serious problems such as drug resistance. Introducing dual inhibiting effect is a valid approach to solve this trouble and bring advantages including wide adaptability, favorable safety and superiority of combination. We started from potential DNA Gyrase inhibitory backbone isatin to develop oxoindolin derivatives as atypical dual Gyrase (major) and FabH (assistant) inhibitors via a two-round screening. Aiming at blocking both duplication (Gyrase) and survival (FabH), most of synthesized compounds indicated potency against Gyrase and some of them inferred favorable inhibitory effect on FabH. The top hit I18 suggested comparable Gyrase inhibitory activity (IC50 = 0.025 µM) and antibacterial effect with the positive control Novobiocin (IC50 = 0.040 µM). FabH inhibitory activity (IC50 = 5.20 µM) was also successfully introduced. Docking simulation hinted possible important interacted residues and binding patterns for both target proteins. Adequate Structure-Activity Relation discussions provide the future orientations of modification. With high potency, low initial toxicity and dual inhibiting strategy, advanced compounds with therapeutic methods will be developed for clinical application.

Introducing Broadened Antibacterial Activity to Rhodanine Derivatives Targeting Enoyl-Acyl Carrier Protein Reductase.

Broadened antibacterial activity was introduced to rhodanine derivatives targeting Mycobacterial tuberculosis enoyl-acyl carrier protein reductase (Mtb InhA) by recruiting feature of xacins to bring DNA Gyrase B inhibitory capability. This is significant for preventing further bacterial injections in the tuberculosis treatment. The most potent compound Cy14 suggested comparable bioactivity (IC50 = 3.18 µM for Mtb InhA; IC50 = 10 nM for DNA Gyrase B) with positive controls. Structure-activity relationship discussion and molecular docking model revealed the significance of rhodanine moiety and derived methoxyl on meta-position, pointing out orientations for future modification.

Developing potential Helicobacter pylori urease inhibitors from novel oxoindoline derivatives: Synthesis, biological evaluation and in silico study.

By recruiting the important moiety from Shikonin, a series of novel oxoindoline derivatives S1-S20 have been synthesized for inhibiting H. pylori urease. The most potent compound S18 displayed better activity (IC50 = 0.71 µM; MIC = 0.48 µM) than the positive controls AHA (IC50 = 17.2 µM) and Metronidazole (MIC = 31.3 µM). With low cytotoxicity, it showed considerable potential for further development. Docking simulation revealed the possible binding pattern of this series. 3D QSAR model was built to discuss SAR and give useful hints for future modification.

[Curcumin improves the impaired working memory in cerebral ischemia-reperfusion rats by inhibiting proinflammatory cytokines].

OBJECTIVE: To investigate the ameliorative effect of curcumin pretreatment against impaired spatial working memory on global cerebral ischemia-reperfusion rats and to explore its mechanism. METHODS: After trained on a modified T-maze, 120 adult SD rats were randomly divided into 5 groups: sham group (S group), cerebral ischemia-reperfusion group (IR group), curcumin group (C group), LPS group (L group) and curcumin+LPS group (C+L group). Rats were treated with drugs or vehicles 1 h before 10 min global cerebral ischemia. Six rats in each group 7 days after reperfusion were tested in T-maze. Six rats in each group were sacrificed at 2 h, 1, 3 and 7 d after reperfusion and their serum or brains were harvested. Brain sections were stained with HE or toluidine blue and neuronal damage was quantified by the average neuronal density of CA1 area. Immunohistochemical staining for hippocampal IL-1ß and TNF-α was carried out, levels of serum IL-1ß and TNF-α was detected using ELISA procedure. RESULTS: Compared with S group, percentage of T-maze correct responses was decreased (88% ± 12% vs 69% ± 8%, P < 0.05), an extensive pyramidal neurons loss in CA1 area was observed, level of IL-1ß (0.26 ± 0.04 vs 0.53 ± 0.06, P < 0.05;48 ± 13 vs 161 ± 31, P < 0.05) and TNF-α (40.244 ± 0.025 vs 0.418 ± 0.036, P < 0.05; 33 ± 4 vs 85 ± 15, P < 0.05) in hippocampi or serum was increased in IR group. Compared with IR group, percentage of T-maze correct responses was increased (78% ± 13%) and average pyramidal neuronal density in CA1 area was increased with an decrease in hippocampi or serum IL-1ß (0.44 ± 0.09, 72 ± 19) and TNF-α (0.307 ± 0.047, 57 ± 14) in C group(P < 0.05). Compared with IR group, percentage of T-maze correct responses (61% ± 6%) was decreased with IL-1ß (0.86 ± 0.13, 331 ± 51), TNF-α (0.735 ± 0.059, 185 ± 20) in hippocampi and serum was increased in L group (P < 0.05). Compared with L group, percentage of T-maze correct responses (69% ± 12%) and average pyramidal neuronal density in CA1 area was increased with IL-1ß (0.69 ± 0.09, 246 ± 24), TNF-α(0.586 ± 0.047, 105 ± 25) in hippocampi and serum was decreased in C+L group (P < 0.05). CONCLUSION: Curcumin pretreatment improves the impaired spatial working memory in global cerebral ischemia-reperfusion rats by inhibiting proinflammatory cytokines.

SLMFNet: Enhancing land cover classification of remote sensing images through selective attentions and multi-level feature fusion.

Land cover classification (LCC) is of paramount importance for assessing environmental changes in remote sensing images (RSIs) as it involves assigning categorical labels to ground objects. The growing availability of multi-source RSIs presents an opportunity for intelligent LCC through semantic segmentation, offering a comprehensive understanding of ground objects. Nonetheless, the heterogeneous appearances of terrains and objects contribute to significant intra-class variance and inter-class similarity at various scales, adding complexity to this task. In response, we introduce SLMFNet, an innovative encoder-decoder segmentation network that adeptly addresses this challenge. To mitigate the sparse and imbalanced distribution of RSIs, we incorporate selective attention modules (SAMs) aimed at enhancing the distinguishability of learned representations by integrating contextual affinities within spatial and channel domains through a compact number of matrix operations. Precisely, the selective position attention module (SPAM) employs spatial pyramid pooling (SPP) to resample feature anchors and compute contextual affinities. In tandem, the selective channel attention module (SCAM) concentrates on capturing channel-wise affinity. Initially, feature maps are aggregated into fewer channels, followed by the generation of pairwise channel attention maps between the aggregated channels and all channels. To harness fine-grained details across multiple scales, we introduce a multi-level feature fusion decoder with data-dependent upsampling (MLFD) to meticulously recover and merge feature maps at diverse scales using a trainable projection matrix. Empirical results on the ISPRS Potsdam and DeepGlobe datasets underscore the superior performance of SLMFNet compared to various state-of-the-art methods. Ablation studies affirm the efficacy and precision of SAMs in the proposed model.

Children's bone age development is delayed with increasing altitude: a multicenter study.

OBJECTIVES: To investigate the bone age (BA) characteristics of children living at high-altitude regions and determine the impact of altitude on the development of BA. METHODS: From June 2014 to July 2022, 1,318 children with left hand-wrist radiographs were retrospectively enrolled from three different geographical altitudes (Beijing 43.5 m above sea level [asl], Lhasa 3650 m asl, and Nagqu 4500 m asl). The predicted age difference (PAD), defined as the difference between BA and chronologic age (CA), was considered the indicator for delayed or advanced growth. The PAD of children from the three regions in total and according to different age groups, genders, and ethnicities were compared. The linear regression model was used to assess the effect of altitude on PAD. RESULTS: A total of 1284 children (CA: 12.00 [6.45, 15.72] years; male: 837/1284, 65.2%) were included in the study with 407 from Beijing, 491 from Lhasa, and 386 from Nagqu. The PAD for Beijing, Lhasa, and Nagqu were 0.1 [-0.30, 0.65], -0.40 [-1.20, 0.27], and -1.42 [-2.32, -0.51] years, respectively. A linear regression analysis showed that altitude significantly contributed to PAD (compared to Beijing, Lhasa coefficient = -0.57, P < 0.001; Nagqu coefficient = -1.55, P < 0.001). CONCLUSIONS: High altitude might be an independent contributor to the delayed BA development of children. ADVANCES IN KNOWLEDGE: The impact of altitude on BA development was revealed for the first time, highlighting the necessity of considering the altitude of the area when evaluating BA development for children residing in high-altitude regions.

An artificial intelligence-based bone age assessment model for Han and Tibetan children.

Background: Manual bone age assessment (BAA) is associated with longer interpretation time and higher cost and variability, thus posing challenges in areas with restricted medical facilities, such as the high-altitude Tibetan Plateau. The application of artificial intelligence (AI) for automating BAA could facilitate resolving this issue. This study aimed to develop an AI-based BAA model for Han and Tibetan children. Methods: A model named "EVG-BANet" was trained using three datasets, including the Radiology Society of North America (RSNA) dataset (training set n = 12611, validation set n = 1425, and test set n = 200), the Radiological Hand Pose Estimation (RHPE) dataset (training set n = 5491, validation set n = 713, and test set n = 79), and a self-established local dataset [training set n = 825 and test set n = 351 (Han n = 216 and Tibetan n = 135)]. An open-access state-of-the-art model BoNet was used for comparison. The accuracy and generalizability of the two models were evaluated using the abovementioned three test sets and an external test set (n = 256, all were Tibetan). Mean absolute difference (MAD) and accuracy within 1 year were used as indicators. Bias was evaluated by comparing the MAD between the demographic groups. Results: EVG-BANet outperformed BoNet in the MAD on the RHPE test set (0.52 vs. 0.63 years, p < 0.001), the local test set (0.47 vs. 0.62 years, p < 0.001), and the external test set (0.53 vs. 0.66 years, p < 0.001) and exhibited a comparable MAD on the RSNA test set (0.34 vs. 0.35 years, p = 0.934). EVG-BANet achieved accuracy within 1 year of 97.7% on the local test set (BoNet 90%, p < 0.001) and 89.5% on the external test set (BoNet 85.5%, p = 0.066). EVG-BANet showed no bias in the local test set but exhibited a bias related to chronological age in the external test set. Conclusion: EVG-BANet can accurately predict the bone age (BA) for both Han children and Tibetan children living in the Tibetan Plateau with limited healthcare facilities.

Dissolvable microneedle-based wound dressing transdermally and continuously delivers anti-inflammatory and pro-angiogenic exosomes for diabetic wound treatment.

Due to overactive inflammation and hindered angiogenesis, self-healing of diabetic wounds (DW) remains challenging in the clinic. Platelet-derived exosomes (PLT-Exos), a novel exosome capable of anti-inflammation and pro-angiogenesis, show great potential in DW treatment. However, previous administration of exosomes into skin wounds is topical daub or intradermal injection, which cannot intradermally deliver PLT-Exos into the dermis layer, thus impeding its long-term efficacy in anti-inflammation and pro-angiogenesis. Herein, a dissolvable microneedle-based wound dressing (PLT-Exos@ADMMA-MN) was developed for transdermal and long-term delivery of PLT-Exos. Firstly, a photo-crosslinking methacrylated acellular dermal matrix-based hydrogel (ADMMA-GEL), showing physiochemical tailorability, fast-gelling performance, excellent biocompatibility, and pro-angiogenic capacities, was synthesized as a base material of our dressing. For endowing the dressing with anti-inflammation and pro-angiogenesis, PLT-Exos were encapsulated into ADMMA-GEL with a minimum effective concentration determined by our in-vitro experiments. Then, in-vitro results show that this dressing exhibits excellent properties in anti-inflammation and pro-angiogenesis. Lastly, in-vivo experiments showed that this dressing could continuously and transdermally deliver PLT-Exos into skin wounds to switch local macrophage into M2 phenotype while stimulating neovascularization, thus proving a low-inflammatory and pro-angiogenic microenvironment for DW healing. Collectively, this study provides a novel wound dressing capable of suppressing inflammation and stimulating vascularization for DW treatment.

SARS-CoV-2 infection-induced immunity reduces rates of reinfection and hospitalization caused by the Delta or Omicron variants.

During a pandemic, effective vaccines are typically in short supply, particularly at onset intervals when the wave is accelerating. We conducted an observational, retrospective analysis of aggregated data from all patients who tested positive for SARS-CoV-2 during the waves caused by the Delta and Omicron variants, stratified based on their known previous infection and vaccination status, throughout the University of Texas Medical Branch (UTMB) network. Next, the immunity statuses within each medical parameter were compared to naïve individuals for the effective decrease of occurrence. Lastly, we conducted studies using mice and pre-pandemic human samples for IgG responses to viral nucleocapsid compared to spike protein toward showing a functional component supportive of the medical data results in relation to the immunity types. During the Delta and Omicron waves, both infection-induced and hybrid immunities were associated with a trend of equal or greater decrease of occurrence than vaccine-induced immunity in hospitalizations, intensive care unit admissions, and deaths in comparison to those without pre-existing immunity, with hybrid immunity often trending with the greatest decrease. Compared to individuals without pre-existing immunity, those vaccinated against SARS-CoV-2 had a significantly reduced incidence of COVID-19, as well as all subsequent medical parameters. Though vaccination best reduces health risks associated with initial infection toward acquiring immunity, our findings suggest infection-induced immunity is as or more effective than vaccination in reducing the severity of reinfection from the Delta or Omicron variants, which should inform public health response at pandemic onset, particularly when triaging towards the allotment of in-demand vaccinations.

Design of Replication-Competent VSV- and Ervebo-Vectored Vaccines Against SARS-CoV-2.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health emergency. Several vaccine candidates have been developed in response to the COVID-19 pandemic. One approach is to construct live-recombinant viruses expressing the SARS-CoV-2 spike protein (S) as vaccine candidates. The vesicular stomatitis virus (VSV) vector is a mature vaccine platform which was successfully developed as a vaccine against Ebola virus (EBOV), leading to its licensure by the Food and Drug Administration (FDA) in December 2019. Based on this work, we developed two live, replication-competent VSV-vectored vaccines against SARS-CoV-2: (1) a VSV expressing the S protein of SARS-CoV-2 and (2) a bivalent VSV expressing the S protein of SARS-CoV-2 and the glycoprotein (GP) of EBOV. This protocol describes the methodologies for the design, cloning, rescue, and preparation of these recombinant VSV vaccines.

The RNA-binding protein IMP2 drives a stromal-Th17 cell circuit in autoimmune neuroinflammation.

Stromal cells are emerging as key drivers of autoimmunity, partially because they produce inflammatory chemokines that orchestrate inflammation. Chemokine expression is regulated transcriptionally but also through posttranscriptional mechanisms, the specific drivers of which are still incompletely defined. CCL2 (MCP1) is a multifunctional chemokine that drives myeloid cell recruitment. During experimental autoimmune encephalomyelitis (EAE), an IL-17-driven model of multiple sclerosis, CCL2 produced by lymph node (LN) stromal cells was essential for immunopathology. Here, we showed that Ccl2 mRNA upregulation in human stromal fibroblasts in response to IL-17 required the RNA-binding protein IGF-2 mRNA-binding protein 2 (IGF2BP2, IMP2), which is expressed almost exclusively in nonhematopoietic cells. IMP2 binds directly to CCL2 mRNA, markedly extending its transcript half-life, and is thus required for efficient CCL2 secretion. Consistent with this, Imp2-/- mice showed reduced CCL2 production in LNs during EAE, causing impairments in monocyte recruitment and Th17 cell polarization. Imp2-/- mice were fully protected from CNS inflammation. Moreover, deletion of IMP2 after EAE onset was sufficient to mitigate disease severity. These data showed that posttranscriptional control of Ccl2 in stromal cells by IMP2 was required to permit IL-17-driven progression of EAE pathogenesis.

Mapping cross-variant neutralizing sites on the SARS-CoV-2 spike protein.

The emergence of multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern threatens the efficacy of currently approved vaccines and authorized therapeutic monoclonal antibodies (MAbs). It is hence important to continue searching for SARS-CoV-2 broadly neutralizing MAbs and defining their epitopes. Here, we isolate 9 neutralizing mouse MAbs raised against the spike protein of a SARS-CoV-2 prototype strain and evaluate their neutralizing potency towards a panel of variants, including B.1.1.7, B.1.351, B.1.617.1, and B.1.617.2. By using a combination of biochemical, virological, and cryo-EM structural analyses, we identify three types of cross-variant neutralizing MAbs, represented by S5D2, S5G2, and S3H3, respectively, and further define their epitopes. S5D2 binds the top lateral edge of the receptor-binding motif within the receptor-binding domain (RBD) with a binding footprint centred around the loop477-489, and efficiently neutralizes all variant pseudoviruses, but the potency against B.1.617.2 was observed to decrease significantly. S5G2 targets the highly conserved RBD core region and exhibits comparable neutralization towards the variant panel. S3H3 binds a previously unreported epitope located within the evolutionarily stable SD1 region and is able to near equally neutralize all of the variants tested. Our work thus defines three distinct cross-variant neutralizing sites on the SARS-CoV-2 spike protein, providing guidance for design and development of broadly effective vaccines and MAb-based therapies.

Strain effect in Pd@PdAg twinned nanocrystals towards ethanol oxidation electrocatalysis.

The strain effect is a critical knob to tune the catalytic performance and has received unprecedented research interest recently. However, it is difficult to distinguish the strain effect from the synergistic effect, especially in alloyed catalysts. Here we have synthesized Pd@PdAg icosahedra and {111} truncated bi-pyramids with only different surface strains between them as electrocatalysts for the ethanol oxidation reaction (EOR). Due to the same exposed facets and compositions of the two electrocatalysts, their EOR performances are mainly determined by the surface strains of PdAg alloys. These two electrocatalysts provide a perfect model to investigate the role of the strain effect in tuning the EOR performance. It is indicated that Pd@PdAg {111} truncated bi-pyramids with a surface strain of 0.3% show better catalytic activity and durability than Pd@PdAg icosahedra with a surface strain of 2.1% including commercial Pd/C. Density functional theory (DFT) calculations reveal that the lowered d-band center of 0.3% strained PdAg alloys relative to 2.1% strained ones reduced the adsorption energy of the acetate-evolution key intermediate *CH3CO, thereby promoting the enhancement in the catalytic performance of Pd@PdAg nanocrystals for the EOR. Electrochemical analysis further verifies this demonstration on the key role of the strain effect in PdAg alloys for tuning catalytic performance.

IL-17-dependent fibroblastic reticular cell training boosts tissue protective mucosal immunity through IL-10-producing B cells.

Prior experience of pathogen-associated stimuli reduces morbidity and mortality to newly encountered infections through innate immune training, which can be enhanced by childhood vaccination. Fibroblastic reticular cells (FRCs) are stromal cells in lymphoid organs that support lymphocyte localization and survival and modulate adaptive immune responses. IL-17 signaling is important for FRC metabolism and proliferation during inflammatory responses. Here, we show that FRC-intrinsic IL-17 signaling was required for protective antibody-mediated immunity to the gut bacterial pathogen Citrobacter rodentium. We asked whether prior activation of FRC through nonspecific inflammatory "training" of the gut would alter subsequent immune response to C. rodentium. Inflammatory training increased the number of activated FRC in mesenteric LN (MLN) and enhanced the antibody response to C. rodentium in an IL-17­dependent manner. FRC demonstrated cardinal features of innate immune training, including increased epigenetic markers of activation and increased metabolic response to infection. Enhanced responses were still evident 6 weeks after training. The kinetics of bacterial infection were not changed by inflammatory training, but colon inflammation was paradoxically reduced. Mechanistically, IL-10 production by activated B cells was required for colon protective effects of inflammatory training. Enhancing tissue protective B cell responses thus led to increased production of antibody and IL-10, allowing clearance of infection with reduced tissue inflammation. These data identify a new mode of immune training through FRC to modulate future adaptive responses and better preserve host health.

Poly(ethylene glycol) dimethyl ether mediated oxidative scission of aromatic olefins to carbonyl compounds by molecular oxygen.

A simple, and practical oxidative scission of aromatic olefins to carbonyl compounds using O2 as the sole oxidant with poly(ethylene glycol) dimethyl ether as a benign solvent has been developed. A wide range of monosubstituted, gem-disubstituted, 1,2-disubstituted, trisubstituted and tetrasubstituted aromatic olefins was successfully converted into the corresponding aldehydes and ketones in excellent yields even with gram-scale reaction. Some control experiments were also conducted to support a possible reaction pathway.