Akt, also known as protein kinase B, plays key roles in cell proliferation, survival and metabolism. Akt hyperactivation contributes to many pathophysiological conditions, including human cancers, ...and is closely associated with poor prognosis and chemo- or radiotherapeutic resistance. Phosphorylation of Akt at S473 (ref. 5) and T308 (ref. 6) activates Akt. However, it remains unclear whether further mechanisms account for full Akt activation, and whether Akt hyperactivation is linked to misregulated cell cycle progression, another cancer hallmark. Here we report that Akt activity fluctuates across the cell cycle, mirroring cyclin A expression. Mechanistically, phosphorylation of S477 and T479 at the Akt extreme carboxy terminus by cyclin-dependent kinase 2 (Cdk2)/cyclin A or mTORC2, under distinct physiological conditions, promotes Akt activation through facilitating, or functionally compensating for, S473 phosphorylation. Furthermore, deletion of the cyclin A2 allele in the mouse olfactory bulb leads to reduced S477/T479 phosphorylation and elevated cellular apoptosis. Notably, cyclin A2-deletion-induced cellular apoptosis in mouse embryonic stem cells is partly rescued by S477D/T479E-Akt1, supporting a physiological role for cyclin A2 in governing Akt activation. Together, the results of our study show Akt S477/T479 phosphorylation to be an essential layer of the Akt activation mechanism to regulate its physiological functions, thereby providing a new mechanistic link between aberrant cell cycle progression and Akt hyperactivation in cancer.
A visible light‐induced reductive addition of 1°, 2° and 3° alkyl iodides to ethenesulfonyl fluoride, employing Hantzsch ester as a hydrogen source at room temperature was developed. This method ...featured a wide substrate scope and great functional group compatibility, providing facile and robust process to alkyl sulfonyl fluorides including enzyme inhibitors, natural products and drugs derivatives in up to 99% yield. Further derivatization of resultant aliphatic sulfonyl fluorides was also achieved through sulfur fluoride exchange (SuFEx) reactions to deliver sulfonates and sulfonamides as privileged motifs for medicinal chemistry.
The worldwide dissemination of
isolates is a significant public health concern, as these organisms possess a unique capacity to acquire genetic elements encoding both resistance and hypervirulence. ...This study aims to investigate the epidemiological, resistance, and virulence characteristics of
isolates that carry both virulence plasmids and
genes in a tertiary hospital in China.
A total of 217 clinical isolates of carbapenem-resistant
(CRKP) were collected between April 2020 and March 2022. The antimicrobial susceptibility test was conducted to evaluate the drug resistance profile. All isolates were screened for the presence of genes encoding carbapenemases (
,
,
,
, and
), ESBLs genes (
,
,
), and virulence plasmid pLVPK-borne genes (
,
,
,
, and
) using polymerase chain reaction (PCR) amplification. Clonal lineages were assigned using multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). The plasmid incompatibility groups were identified using PCR-based replicon typing (PBRT). The transferability of carbapenemase-encoding plasmids and pLVPK-like virulence plasmids was assessed via conjugation. The plasmid location of
was determined using S1-Pulsed Field Gel Electrophoresis (S1-PFGE) and southern blotting hybridization. The virulence potential of the isolates was assessed using the string test, capsular serotyping, serum killing assay and a Galleria mellonella larval infection model.
Of the 217 CRKP clinical isolates collected, 23% were identified as carrying
genes. All
isolates exhibited resistance to commonly used clinical antimicrobial agents, except for ceftazidime/avibactam, colistin, tigecycline, trimethoprim-sulfamethOXAzole, polymyxin B, and nitrofurantoin. The main common OXA-48-like carbapenemase enzymes were found to be
and
. MLST and PFGE fingerprinting analysis revealed clonal transmission and plasmid transmission. OXA-48-like producing CRKP isolates mainly clustered in K64 ST11 and K47 ST15. Results of the string Test, serum killing assay (
) and
infection model (
) indicated hypervirulence. PBRT showed that the
and
producing hypervirulent carbapenem-resistant
(Hv-CRKP) were mainly carried on ColE-type, IncF, and IncX3. Eight clinical isolates of hv-CRKP were identified as carrying three carbapenem-resistant genes (
,
, and
). Moreover, Southern blotting hybridization revealed that all eight isolates had a pLVPK-like virulent plasmid (138.9-216.9 kb) with an uneven number and size of plasmid.
In our investigation, we have observed the emergence of hv-CRKP carrying
genes, which identified two genetic relationships: clonal transmission and plasmid transmission. PBRT analysis showed that these genes were mainly carried on ColE-type, IncF, and IncX3 plasmids. These isolates have been shown to be hypervirulent
and
. Additionally, eight clinical isolates of hv-CRKP were identified as carrying three carbapenem-resistant genes (
,
, and
) and carrying a pLVPK-like virulent plasmid. Hence, our findings highlight the need for further investigation and active surveillance of hypervirulent OXA-48-like producing Hv-CRKP isolates to control their transmission.
A water-soluble polysaccharide, designated as LBP-3, was isolated and purified from Lycium barbarum. Chemical analysis indicated that LBP-3 was composed of arabinose and galactose at a molar ratio of ...1.00:1.56. The average molecular weight of LBP-3 was 6.74 × 104 Da. The structural features of LBP-3 were investigated by Fourier-transform infrared spectroscopy (FT-IR), methylation, and nuclear magnetic resonance (NMR). LBP-3 is a highly branched polysaccharide with a backbone of 1, 3-linked β-Galp, which is partially substituted at C-6. The branches contain 1, 5-linked α-Araf, 1, 6-linked β-Galp, 1, 3-linked α-Araf, and 1, 4-linked α-Araf. In vitro studies revealed that LBP-3 induced a concentration-dependent decrease in the levels of Aβ42/Aβ40 in N2a/APP695 cells. Proteomic analysis was conducted to investigate the potential molecular mechanism underlying the neuroprotective effect of LBP-3, and the results suggested that LBP-3 might have the potential for the treatment of AD.
•A novel structure LBP-3 was separated from Lycium barbarum polysaccharides.•LBP-3 have potential for the treatment of AD.•Proteomic analysis was conducted to investigate the potential mechanism.
The emerging 5G wireless networks are envisioned to provide dramatically increased network capacity by using significantly expanded frequency band. With already crowded radio spectrum, utilization ...efficiency of frequency resources needs to be substantially improved in 5G to accommodate more users. On the other hand, the extremely wide and dynamic spectrum resources required by 5G create a significant opportunity to develop advanced resource management techniques. In this article, we propose a novel architecture to support 5G spectrum management, which uses various requirements for QoE as the design objective. With the proposed architecture, an intelligent and dynamic QoE-driven spectrum assignment scheme for 5G is introduced. The proposed scheme accomplishes dynamic spectrum assignment for each macrocell by utilizing global information that reflects the dynamic QoE requirement. In addition, we effectively allocate the spectrum bands for various devices relying on the reconfigurable RF front-end of SDR-based devices. The presented architecture is expected to support dynamic and efficient spectrum management for 5G wireless networks. Meanwhile, the intelligent and dynamic QoE-driven spectrum assignment scheme is expected to achieve an improved spectrum utilization rate, which could directly accelerate the development of 5G wireless networks.
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•Studied transition metals Cr, Mn, Fe, Co, Ni, Cu, and Zn.•Observed synergy between CuO and CeO2.•Cu–O–Ce interface provided the most active sites.
Selective catalytic reduction (SCR) ...reduces oxynitrides from power plant and vehicle emissions, and enhancements in efficiency would lessen pollution further. We prepared a series of transition metal (TM) doped CeO2 catalysts by impregnating them with vermiculite (VMT) as a carrier for reducing NOx by SCR with carbon monoxide (CO–SCR). The catalyst performance was in the following order: Zn < Cr < Fe < no dopant < Mn < Ni < Co < Cu. In other words, Mn, Ni, Co, and Cu greatly promoted NO conversion compared with Ce/VMT alone, whereas Zn, Cr, and Fe dopants hindered NO conversion. We applied density functional theory (DFT) by structural optimization and potential configuration analyses of CeO2 (111) and TM–CeO2 (111), which enabled us to propose the reaction pathway and the potential energy distribution of the transition state. Our DFT analyses are in accordance with the sequence of the NO + CO reaction. The performance of the Cu catalyst was superior to the others. The CeO2 (111) lattice plane is primarily in the cerium species, whereas the Cu–O–Ce interface forms in two phases, which indicates a complex interplay between the copper and cerium. Furthermore, the catalyst has numerous surface oxygen vacancies (Ovs) and active *O species, and exhibits an impressive reduction capacity: the NO conversion reaches 100% with a gas hourly space velocity of 102,000 h−1 at 300 °C. The CO–SCR reaction pathway on the Cu–CeO2 (111) surface is as follows: R1: CO + Olattice → Ov; R2: 2NO → *ONNO → N2O + *O; R3: N2O → N2 + *O; R4: *O + CO → CO2; R5: *O + Ov → Olattice. The synergy of the dopants on the CeO2 (111) surface modulated the distribution of active centers in the catalyst, which in turn modulated the catalyst performance. Our research will be useful for flue gas remediation.
In this paper, a newly ring-shaped spoof surface plasmon polaritons (SSPPs) structure is proposed for the construction of bandpass filter (BPF) with combing the short-circuited stubs (SCSs). Compared ...with the conventional rectangular-shaped SSPPs unit, the proposed ring-shaped SSPPs unit has a relative lower cutoff frequency at the same periodic unit size. Moreover, the high-order modes of the ring-shaped SSPPs unit at different height are disperse distribution, which allows it to realize wide stopband suppression. The lower and upper cutoff frequencies of the passband can be respective controlled by structural parameters of SCSs and SSPPs unit. By properly adjusting the height of SSPPs units in conversion parts, a balanced performance between the passband and ultra-wide stopband suppression can be achieved. For verification, a BPF with the frequency from 2 GHz to 5 GHz for Sub-6G application and the stopband reaching 30 GHz is designed. The experimental show that the measured results agree well with the simulated results, validating the proposed structure and design method. The fabricated filter only occupies 1.13λg × 0.23λg, exhibits the advantage of compact size.
A clickable connective hub 1-bromo-2-triazolethane-1-sulfonyl fluoride BTESF (
) was developed and successfully applied for the fluorosulfonylvinylation of a host of primary and secondary cyclic or ...acyclic amines including amino acids and pharmaceuticals. Further antimicrobial experiments revealed that vinyl sulfonyl fluoride functionalized norfloxacin (
), ciprofloxacin (
), and lomefloxacin (
) exhibited 4-fold improved antimicrobial activity against Gram-positive bacteria compared to their parent drugs.
In the CO‐SCR reaction, reducing by‐product N2O formation helps to convert more NO into clean N2, which has a great significance to environmental governance. In this study, the CuCe mixed metal ...oxides with different molar ratios of Cu to Ce were prepared, characterized and evaluated to study the effect on the products of NO reduction by CO. The experimental results showed that the CuCe‐1 : 3 catalyst showed superior NO conversion with over 90 % N2 selectivity in the operating temperature window, and there were no amounts of N2O by‐product at 50–200 °C. The higher oxygen vacancy concentration and appearance of (NO)2 dimer inhibited N2O formation at low temperature. Finally, the reaction paths for the CuCe catalysts generating different products (N2, N2O) were proposed in the CO‐SCR reaction based on in‐situ DRIFTS results.
CO‐SCR Systems: In this study, different ratios of CuCe catalysts were prepared to reduce the by‐product N2O during the CO‐SCR reaction. The CuCe‐1 : 3 catalyst not only exhibited excellent catalytic performance, but also produced no by‐product N2O. The CuCe‐1 : 3 catalyst only generated N2 at low temperature due to its high oxygen vacancy concentration and the presence of (NO)2 dimer. The formation mechanisms of N2 and N2O products are proposed based on in‐situ DRIFTS results.
Infection caused by carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) has become a tricky health care threat in China and KPC-2 enzyme is a main factor mediating resistance to ...carbapenems of
K. pneumoniae
. Here, we report the characterization of the genetic environment of the blaKPC-2 gene in CR-hvKP clinical isolates from South China. Forty-five non-duplicated CR-hvKP isolates collected in Jiangxi Province from 2018 to 2019 were analyzed. Each of them were multidrug-resistant due to the presence not only of blaKPC-2 gene but also of other resistance determinants, including Metallo-β-lactamases (NDM-1), extended-spectrum β-lactamases (TEM-1, CTX-M-14, SHV-1), and plasmid-mediated quinolone resistance determinants (qnrS, aac(6′)-Ib-cr). After plasmid analyses of PCR-based replicon typing (PBRT), mapping PCR, amplicon sequencing, and whole-genome sequencing (WGS) were used to analyze the genetic environment of the blaKPC-2 gene. PCR analysis of pLVPK-like plasmids, Southern Blot, and mouse lethality assay were used to characterize the virulence phenotype of
K. pneumoniae
. Multilocus sequence typing (MLST) analysis showed ST11 CR-hvKP was the predominant clone. In conclusion, this is the first analysis of diverse genetic structures blaKPC-2 gene in CR-hvKP isolates from south China. Both the NTEKPC-I on the IncF plasmids and pLVPK-like virulence plasmids make contributions to the formation of CR-hvKP especially ST11 which need more attention.
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