The conventional methods for preparing alkyl boronates often necessitate anhydrous and demanding reaction conditions. Herein, a new, operationally simple decarboxylative borylation reaction of ...readily available aliphatic acid derivatives under additive-free visible-light photoredox conditions in nonanhydrous solvents has been described. Primary and secondary alkyl boronates or tetrafluoroborates with various functional groups were prepared accordingly. A catalytic cycle involving alkyl radical reaction with base-activated diboron species has been proposed.
In the past decades, the iridium-catalyzed C–H bond borylation and other newly discovered catalytic borylation reactions have received extensive research interests and developed into a practical ...approach for functionalization of C−H bonds and therefore an effective and versatile tool in synthesis of novel organic materials, natural products and fine chemicals. The advances of this booming field include significant improvements of the venerable iridium-catalyzed borylation and development of other transition-metal, especially the first-row transition-metal catalyzed borylation. More recently, a metal-free catalytic borylation system has been disclosed. These new methodologies has dramatically expanded the substate scope, increased the reaction efficiency, lowered the cost, and more importantly, provided previously unknown complementary chemical and regioselectivity. During these discoveries, novel catalyst design concepts and/or principles have been generated. In this context, this review aims to detail the recent evolution in the exciting research direction, focusing on the discovery and development of new reactivity, new selectivity.
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The gut microbiota benefits humans via short-chain fatty acid (SCFA) production from carbohydrate fermentation, and deficiency in SCFA production is associated with type 2 diabetes mellitus (T2DM). ...We conducted a randomized clinical study of specifically designed isoenergetic diets, together with fecal shotgun metagenomics, to show that a select group of SCFA-producing strains was promoted by dietary fibers and that most other potential producers were either diminished or unchanged in patients with T2DM. When the fiber-promoted SCFA producers were present in greater diversity and abundance, participants had better improvement in hemoglobin A1c levels, partly via increased glucagon-like peptide-1 production. Promotion of these positive responders diminished producers of metabolically detrimental compounds such as indole and hydrogen sulfide. Targeted restoration of these SCFA producers may present a novel ecological approach for managing T2DM.
Treatment with immune checkpoint blockade (ICB) has revolutionized cancer therapy. Until now, predictive biomarkers
and strategies to augment clinical response have largely focused on the T cell ...compartment. However, other immune subsets may also contribute to anti-tumour immunity
, although these have been less well-studied in ICB treatment
. A previously conducted neoadjuvant ICB trial in patients with melanoma showed via targeted expression profiling
that B cell signatures were enriched in the tumours of patients who respond to treatment versus non-responding patients. To build on this, here we performed bulk RNA sequencing and found that B cell markers were the most differentially expressed genes in the tumours of responders versus non-responders. Our findings were corroborated using a computational method (MCP-counter
) to estimate the immune and stromal composition in this and two other ICB-treated cohorts (patients with melanoma and renal cell carcinoma). Histological evaluation highlighted the localization of B cells within tertiary lymphoid structures. We assessed the potential functional contributions of B cells via bulk and single-cell RNA sequencing, which demonstrate clonal expansion and unique functional states of B cells in responders. Mass cytometry showed that switched memory B cells were enriched in the tumours of responders. Together, these data provide insights into the potential role of B cells and tertiary lymphoid structures in the response to ICB treatment, with implications for the development of biomarkers and therapeutic targets.
High-resolution observations of the solar chromosphere and transition region often reveal surge-like oscillatory activities above sunspot light bridges (LBs). These oscillations are often interpreted ...as intermittent plasma jets produced by quasi-periodic magnetic reconnection. We have analyzed the oscillations above an LB in a sunspot using data taken by the Interface Region Imaging Spectrograph. The chromospheric 2796 images show surge-like activities above the entire LB at any time, forming an oscillating wall. Within the wall we often see that the core of the Mg ii k 2796.35 line first experiences a large blueshift, and then gradually decreases to zero shift before increasing to a redshift of comparable magnitude. Such a behavior suggests that the oscillations are highly nonlinear and likely related to shocks. In the 1400 passband, which samples emission mainly from the Si iv ion, the most prominent feature is a bright oscillatory front ahead of the surges. We find a positive correlation between the acceleration and maximum velocity of the moving front, which is consistent with numerical simulations of upward propagating slow-mode shock waves. The Si iv 1402.77 line profile is generally enhanced and broadened in the bright front, which might be caused by turbulence generated through compression or by the shocks. These results, together with the fact that the oscillation period stays almost unchanged over a long duration, lead us to propose that the surge-like oscillations above LBs are caused by shocked p-mode waves leaked from the underlying photosphere.
Disruption of the gut microbiota by high-fat diet (HFD) has been implicated in the development of obesity. It remains to be elucidated whether the HFD-induced shifts occur at the phylum level or ...whether they can be attributed to specific phylotypes; additionally, it is unclear to what extent the changes are reversible under normal chow (NC) feeding. One group (diet-induced obesity, DIO) of adult C57BL/6J mice was fed a HFD for 12 weeks until significant obesity and insulin resistance were observed, and then these mice were switched to NC feeding for 10 weeks. Upon switching to NC feeding, the metabolic deteriorations observed during HFD consumption were significantly alleviated. The second group (control, CHO) remained healthy under continuous NC feeding. UniFrac analysis of bar-coded pyrosequencing data showed continued structural segregation of DIO from CHO on HFD. At 4 weeks after switching back to NC, the gut microbiota in the DIO group had already moved back to the CHO space, and continued to progress along the same age trajectory and completely converged with CHO after 10 weeks. Redundancy analysis identified 77 key phylotypes responding to the dietary perturbations. HFD-induced shifts of these phylotypes all reverted to CHO levels over time. Some of these phylotypes exhibited robust age-related changes despite the dramatic abundance variations in response to dietary alternations. These findings suggest that HFD-induced structural changes of the gut microbiota can be attributed to reversible elevation or diminution of specific phylotypes, indicating the significant structural resilience of the gut microbiota of adult mice to dietary perturbations.
Abstract
We investigate the peak flux energy spectrum of 458 solar energetic electron (SEE) events with a clear velocity dispersion detected at energies from ≤4.2 to ≥108 keV by Wind/3DP from 1994 ...December through 2019 December, utilizing a pan-spectrum fitting method. According to the fitted spectral parameters, these 458 events are self-consistently classified into five spectral types: 304 downward double-power-law (DDPL) events, 32 upward double-power-law (UDPL) events, 23 single-power-law (SPL) events, 44 Ellison–Ramaty (ER) events, and 55 logarithmic–parabola (LP) events. The DDPL events can be further divided into two types: 231
DDPL
E
B
≥
20
keV
events and 73
DDPL
E
B
<
20
keV
events, since their break energy
E
B
exhibits a double-peak distribution separated by a dip at ∼20 keV. The
DDPL
E
B
<
20
keV
(
DDPL
E
B
≥
20
keV
) events show a power-law spectral index of
2.0
−
0.2
+
0.2
(
2.1
−
0.3
+
0.3
) at energies below
E
B
=
5.6
−
2.4
+
2.3
(
61
−
12
+
23
) keV and an index of
3.3
−
0.3
+
0.5
(
3.9
−
0.7
+
0.6
) at energies above. The UDPL events have a spectral index of
3.0
−
0.3
+
0.3
at energies below
E
B
=
5.1
−
1.8
+
4.2
keV and an index of
2.2
−
0.3
+
0.2
at energies above. The SPL events exhibit a spectral index of
2.8
−
0.2
+
0.5
. The ER events show a spectral index of
1.9
−
0.3
+
0.3
at energies below
E
c
=
31
−
11
+
19
keV. The LP events are characterized by a spectral slope of
1.8
−
0.3
+
0.4
(
3.6
−
0.5
+
0.7
) at 2.8 keV (108 keV). The six spectral types also behave differently in the relationship between spectral parameters and in solar cycle variations. The spectral shape of most SEE events appears to be unrelated to the estimated electron path lengths. These results suggest that the formation of SEE events can involve complex processes/sources.
Abstract
We investigate the hard X-ray (HXR) flare-associated “prompt” solar energetic electron (SEE) 2013 November 12 event with joint EUV jet observations from Solar Dynamics ...Observatory/Atmospheric Imaging Assembly and STEREO-A/EUVI. The SEE energy spectrum observed by Wind/3D Plasma and Energetic Particle shows a triple-power-law shape with a low-energy break of 10.0 ± 1.7 keV and a high-energy break of 56.6 ± 8.9 keV, which has never been reported before for jet-related SEE events. Associated HXR emissions observed by RHESSI and FGST/Gamma-ray Burst Monitor show three distinctive peaks with different spectral indices
β
HPE
of HXR-producing electrons (HPEs) derived by means of thick-target bremsstrahlung model. The high-energy spectral index
β
3
= 4.63 ± 0.65 of SEE is consistent with the HPE spectral index
β
HPE
derived in HXR peak 1 but different from
β
HPE
of HXR peak 2 and peak 3. The main stream of EUV jets reaches a speed of 370 ± 25 km s
−1
after an acceleration of up to 2.9 ± 0.4 km s
−2
in a timescale of ∼2 minutes, and the acceleration time coincides with the decay phase of HXR peak 1. EUV observations from two different viewing directions help to reconstruct the jet magnetic configurations. After the investigation on HXR emissions and jet configurations, the interchange-reconnection model triggered by the emerging flux could be a satisfactory explanation for this jet event.
The realization that cancer progression required the participation of cellular genes provided one of several key rationales, in 1986, for embarking on the human genome project. Only with a reference ...genome sequence could the full spectrum of somatic changes leading to cancer be understood. Since its completion in 2003, the human reference genome sequence has fulfilled its promise as a foundational tool to illuminate the pathogenesis of cancer. Herein, we review the key historical milestones in cancer genomics since the completion of the genome, and some of the novel discoveries that are shaping our current understanding of cancer.
Field carcinogenesis describes the prevalence of tumor-related alterations in normal appearing tissues. Here, we summarize recent efforts in profiling molecular field dynamics for resolving early ...events in cancer evolution. We also highlight gaps in our knowledge of the molecular and cellular heterogeneity of field carcinogenesis and propose directions to tackle these voids using single-cell-based approaches and unique tissue sampling models. By interrogating both the mutagenized epithelium and its microenvironment, we surmise that single-cell-guided studies will help chart the spatiotemporal molecular and cellular "atlas" of field carcinogenesis, will further delineate preneoplastic initiation and progression, and will help identify cancer prevention and early intervention targets.
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