Investigation on the mechanisms of carbapenem resistance among the non-carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae.

Background: In Malaysia, an increase in non-carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae (NC-CRKP) has been observed over the years. Previously, four NC-CRKP with increased susceptibility to ciprofloxacin in the presence of phenylalanine-arginine ß-naphthylamide (PAßN) were identified. However, no contribution of the PAßN-inhibited efflux pump to carbapenem resistance was observed. All four NC-CRKP harboured non-carbapenemase ß-lactamase, with two also exhibiting porin loss. In this study, we further investigated the genomic features and resistance mechanisms of these four isolates. Methods: All four NC-CRKP were subjected to whole-genome sequencing, followed by comparative genomic and phylogenetic analyses. Results: Multi-locus sequence typing (MLST) analysis divided the four NC-CRKP into different sequence types: ST392, ST45, ST14, and ST5947. Neither major nor rare carbapenemase genes were detected. Given the presence of non-carbapenemase ß-lactamase in all isolates, we further investigated the potential mechanisms of resistance by identifying related chromosomal mutations. Deletion mutation was detected in the cation efflux system protein CusF. Insertion mutation was identified in the nickel/cobalt efflux protein RcnA. Missense mutation of ompK36 porin was detected in two isolates, while the loss of ompK36 porin was observed in another two isolates. Conclusions: This study revealed that NC-CRKP may confer carbapenem resistance through a combination of non-carbapenemase ß-lactamase and potential chromosomal mutations including missense mutation or loss of ompK36 porin and/or a frameshift missense mutation in efflux pump systems, such as cation efflux system protein CusF and nickel/cobalt efflux protein RcnA. Our findings highlighted the significance of implementing whole-genome sequencing into clinical practice to promote the surveillance of carbapenem resistance mechanisms among NC-CRKP.

The Role of Alkyl Chains in the Thermoresponse of Supramolecular Network.

Supramolecular materials provide a pathway for achieving precise, highly ordered structures while exhibiting remarkable response to external stimuli, a characteristic not commonly found in covalently bonded materials. The design of self-assembled materials, where properties could be predicted/design from chemical nature of the individual building blocks, hinges upon our ability to relate macroscopic properties to individual building blocks - a feat which has thus far remained elusive. Here, a design approach is demonstrated to chemically engineer the thermal expansion coefficient of 2D supramolecular networks by over an order of magnitude (\boldmath 120 to \boldmath 1000 × 10-6 K-1). This systematic study provides a clear pathway on how to carefully design the thermal expansion coefficient of a 2D molecular assembly. Specifically, a linear relation has been identified between the length of decorating alkyl chains and the thermal expansion coefficient. Counter-intuitively, the shorter the chains the larger is the thermal expansion coefficient. This precise control over thermo-mechanical properties marks a significant leap forward in the de-novo design of advanced 2D materials. The possibility to chemically engineer their thermo-mechanical properties holds promise for innovations in sensors, actuators, and responsive materials across diverse fields.

Ultrasensitive lab-on-paper electrochemical device via heterostructure copper/cuprous sulfide@N-doped C@Au hollow nanoboxes as signal amplifier for alpha-fetoprotein detection.

Rapid and accurate detection of tumor markers at extremely low levels is crucial for the early diagnosis of cancers. In this work, we developed a portable label-free sliding electrochemical paper-based analytical device (ePAD) using copper/cuprous sulfide@N-doped C@Au nanoparticles (Cu/Cu2S@NC@Au) hollow nanoboxes as the signal amplifier for the ultrasensitive detection of alpha-fetoprotein (AFP). Cu/Cu2S@NC nanoboxes were synthesized by sacrificial template and interface reaction methods, on which Au nanoparticles were electrodeposited to construct unique heterostructure for effectively capturing anti-AFP and serving as signal amplifier. The designed ePAD incorporates sliding microfluidic paper chips to form a flexible three-electrode system, enabling highly sensitive detection of AFP with a wide linear range of 0.005-50 ng mL-1 and a low detection limit of 0.62 pg mL-1. The practicality of the prepared ePAD was validated through AFP detection in clinical human serum, which was consistent with chemiluminescence immunoassay. In addition, the developed immunosensor demonstrates excellent specificity, repeatability and stability. This novel platform exhibits significant potential for rapid on-site analysis and point-of-care diagnosis.

Evidence of RNA polymerase III recruitment and transcription at protein-coding gene promoters.

The transcriptional interplay of human RNA polymerase I (RNA Pol I), RNA Pol II, and RNA Pol III remains largely uncharacterized due to limited integrative genomic analyses for all three enzymes. To address this gap, we applied a uniform framework to quantify global RNA Pol I, RNA Pol II, and RNA Pol III occupancies and identify both canonical and noncanonical patterns of gene localization. Most notably, our survey captures unexpected RNA Pol III recruitment at promoters of specific protein-coding genes. We show that such RNA Pol III-occupied promoters are enriched for small nascent RNAs terminating in a run of 4 Ts-a hallmark of RNA Pol III termination indicative of constrained RNA Pol III transcription. Taken further, RNA Pol III disruption generally reduces the expression of RNA Pol III-occupied protein-coding genes, suggesting RNA Pol III recruitment and transcription enhance RNA Pol II activity. These findings resemble analogous patterns of RNA Pol II activity at RNA Pol III-transcribed genes, altogether uncovering a reciprocal form of crosstalk between RNA Pol II and RNA Pol III.

The Versatile Roles of nc886, a Fascinating and Peculiar Regulatory Non-Coding RNA, in Cancer.

This review concerns nc886, a 101-nucleotide non-coding RNA (ncRNA). Because nc886 is transcribed by RNA polymerase III (Pol III) and contains a CpG island in its promoter region, its expression is regulated by several transcription factors and the DNA methylation status. These features drive nc886 expression in two opposing directions during tumorigenesis. The known function of nc886 is to bind to and modulate the activity of target proteins such as PKR, Dicer, and OAS1. By being differentially expressed during tumorigenesis and interacting with these proteins, nc886 plays a role in tumor surveillance, promotes or suppresses tumorigenesis, and influences the efficacy of cancer therapy. The multiple roles of nc886 have been well-documented in the literature. In this review, we have summarized this literature and critically discussed the roles and mechanisms of action of nc886 in various cancers.

Metal-Organic Skeleton-Derived W-Doped Ga2O3-NC Catalysts for Aerobic Oxidative Dehydrogenation of N-Heterocycles.

N-heterocycles with quinoline structures hold significant importance within the chemical and pharmaceutical industries. However, achieving their efficient transformations remains a vital yet challenging endeavor. Herein, a series of W-doped Ga2O3-NC catalysts were synthesized using a Ga-MOF-derived strategy through a simple solvothermal method, with a remarkably high activity and selectivity towards the oxidative dehydrogenation of N-heterocycles. Furthermore, the MOF-derived W-doped Ga2O3-NC catalysts exhibit remarkable substrate tolerance and recyclability. The outstanding catalytic activity was attributed to the robust synergistic interaction between the W species and the Ga2O3-NC carrier, which facilitates the activation of hydrogen atoms in the C-H and C=N bonds on both the oxygen molecule and the substrate to produce H2O2. Additionally, the solvent effect of methanol can significantly enhance dehydrogenation due to its strong ability to donate and accept protons of hydrogen bonding. The present work provides a new approach to MOF-derived non-precious metal catalysts for achieving the efficient oxidation dehydrogenation of N-heterocycles.

Shared Success: Developing a Plan to Evaluate the Implementation and Impact of Medicaid Expansion in North Carolina.

The North Carolina Department of Health and Human Services plans to utilize a data-driven approach to evaluate the impacts of Medicaid expansion in the state. The evaluation plan includes tracking enrollment counts, creating metrics for monitoring of activities, setting measurable goals, and involving trusted community partners throughout.

From Continuous Coverage to Medicaid Expansion: North Carolina's Changing Public Payer Landscape.

During the COVID-19 pandemic, people who may have otherwise lost Medicaid coverage kept it without the need to reapply annually. In 2023, this continuous coverage began to unwind just as North Carolina prepared to expand Medicaid. This issue of the North Carolina Medical Journal tracks the evolution of the state's public payer landscape in unprecedented times of change, with data, analysis, and personal experiences from public health, philanthropy, clinicians, and Medicaid members.

Keeping People Enrolled During Medicaid Expansion and COVID-19 Continuous Coverage Unwinding.

North Carolina is expanding Medicaid insurance coverage while simultaneously removing coverage from individuals as a result of the end of the COVID-19 emergency. These large-scale eligibility changes have created an opportunity for improved processes. North Carolina chose to build upon the existing Medicaid Family Planning program to maintain access to health care while launching Medicaid expansion.

Study on the Flexural Performance of Ultrahigh-Performance Concrete-Normal Concrete Composite Slabs.

In recent years, there have been an increasing number of examples of using ultrahigh-performance concrete (UHPC) as a pavement layer to form an ultrahigh-performance concrete-normal concrete (UHPC-NC) composite structure to improve the bearing capacity of bridges. In order to study the flexural performance of this kind of structure, this research studied the flexural performance of UHPC-NC composite slabs, with UHPC in the compression zone, using experiments, numerical simulation, and theoretical analysis. The results showed the following. Firstly, after the UHPC-NC interface had been chiseled, there was no obvious slip between the two materials during the test, and the composite plate was always subjected to synergistic stress. Secondly, the composite slabs in the compression zone of the UHPC were all subjected to bending failure, and the cooperative working performance of each part under the bending load was good, indicating that the composite slab had a unique failure mode and a high bearing capacity. Thirdly, increasing the thickness of the UHPC significantly improved the flexural capacity of the composite plate, and the maximum increase was about 15%. Increasing the reinforcement ratio of the tensile steel rebars also had an increasing effect, with a maximum increase of about 181%. Finally, the proposed formula for calculating the flexural capacity of composite slabs with UHPC in the compression zone could accurately predict the bearing capacity of said slabs. The calculated results were in good agreement with the experimental values, and the error was small.

Novel Orange-Emitting YPO4:Sm3+/Polymer Nanocomposite Phosphor Films for LED Applications.

A polymer based nanocomposite (NC) material embedded with highly luminescent nanopowders could be promising for replacing traditional luminescent materials from a technological point of view. In this study, we have successfully obtained YPO4: Sm3+ /Polymer nanocomposite phosphor films by embedding YPO4: Sm3+ luminescent nanoparticles (NPs) for orange-light emitting diode (LED) applications. These luminescent NPs were synthesized using the sol gel method in different polymer matrices i.e. polystyrene (PS) and poly (methyl methacrylate) (PMMA) by using direct solution mixing. The structural, morphological, and photoluminescence characteristics of the nano-phosphors and resulting NC films were examined and discussed. The emission spectra of YPO4: Sm3+ (x at.%) nano-phosphors under near-UV excitation at 404 nm were dominated by orange emission attributed to 6H5/2 →   4F7/2 (601 nm) luminescence of Sm3+ ions. The optimum doping concentration of activator Sm3+ in YPO4 matrix was found to be 5 at.%. When the doping concentration of Sm3+ was higher than 5 at.%, concentration quenching occurred. The incorporation of YPO4: Sm3+ NPs into polymer matrices indicated that the NCs retained the original luminescence properties of the luminescent NPs, although a decrease in their emission intensity was observed for the NC films, attributable to a polymer matrix effect, which dominated in PS matrix. The fluorescence decay times of NPs in the NC films were measured and compared to those of proper YPO4: Sm3+ nano-phosphors. A decrease in decay time in NC film was observed due the effective refractive index effect. Temperature-dependent photoluminescence (TDPL) of PMMA NC film was studied in 100-400 K range, investigating the thermal stability of the film. Additionally, CIE coordinates confirmed the red-orange light emission of the prepared phosphors and NC films. The obtained results indicate that the synthesized polymer-nanophosphor NC films are promising candidates for orange-LED applications.

Core-shell Ru@Co2P synergistic catalyst as polysulfides adsorption-catalytic conversion mediator with enhanced redox kinetics in lithium-sulfur batteries.

Lithium-sulfur batteries (LSBs) have emerged as the research hotspot due to their compelling merits, including high specific capacity (1675 mAh g-1), theoretical energy density (2600 Wh kg-1), environmental friendliness, and economic advantages. However, challenges still exist for further application due to their inherent issues such as the natural insulation, shuttle effect, and volume expansion of sulfur cathode during the continuous cycle processes. These factors obstruct the lithium ions (Li+) transfer process and sulfur utilization, resulting in significant impedance and inducing inferior battery performance. Herein, the core-shell nanocube anchoring ruthenium atoms and dicobalt phosphate (Ru@Co2P@NC) were fabricated as the effective catalyst and inhibited barrier for LSBs. On the one hand, the core-shell structure offers numerous channels to expedite Li+ diffusion. On the other hand, ruthenium (Ru) and dicobalt phosphate (Co2P) active sites facilitate the chemical capture of lithium polysulfides (LiPSs), accelerating sluggish kinetics. Ru@Co2P@NC modified cells not only exhibited a high initial specific capacity (1609.35 mAh g-1) at 0.5C and enduring stability with high specific capacity retention of 906.60 mAh g-1 at 0.5C after 400 cycles but also possessed low capacity attenuation rate of 0.07 % per cycle after 600 cycles (1C, Sulfur loading: 1.2 mg). Interestingly, the modified cells demonstrated a high specific capacity and long-cycle stability with high sulfur loading (from 1.984 to 3.137 mg), which provides a promising research approach for high-performance LSBs.

Toward Molecular Textiles: Synthesis and Characterization of Molecular Patches.

This works describes a new step into the assembly of molecular textiles by the use of covalent templating. To establish a well-founded base and to tackle pre-mature obstacles, expected during the fabrication of the desired 2D-material, we opted to investigate the in-solution synthesis of molecular patches e.g. cut-outs of a textile. A bi-functional cross-shaped monomer was designed, synthesized and was in-detail characterized by means of 1H-NMR and chiro-optical spectroscopy. In addition, x-ray structure crystallography was used to assess the absolute configuration. The monomer was used in an in-solution oligomerization to assemble the molecular patches via imine condensation, which revealed the formation of predominately dimeric patches.  The imine-oligomer mixtures were further analyzed by reduction and cleaved to investigate the conditions required post mono-layer assembly. All reaction stages were followed by FT-IR and 1H-NMR analysis. Finally, we address the adsorption of the cross-shaped monomer onto a Au(111) surface, via high vacuum electrospray deposition. The subsequent annealing of the interface induced the on-surface imine condensation reaction, leading to unidimensional oligomers co-adsorbed with clusters of cyclic-dimers. Nc-AFM analysis revealed the tridimensional molecular structures, and together with electrospray deposition technique showed to be a promising pathway to investigate potential monomer candidates.

Highly efficient activation of peroxymonosulfate via KOH-activated Fe@NC for the degradation of bisphenol A.

In this study, the KOH-modified Fe-ZIF-derived carbon materials (Fe@NC-KOH-x) were designed for Fenton-like systems to enhance bisphenol A (BPA) removal from wastewater. Compared with the Fe@NC without KOH activation, the pore structure, BET (Brunner-Emmet-Teller) surface area, and oxygen-containing functional group of KOH-activated Fe@NC-KOH-x are dramatically improved, which increases the adsorption and catalytic performance. The Fe@NC-KOH-900/PMS system showed significant BPA removal reactivity across wide pH ranges and low doses of Fe@NC-KOH-900. Interestingly, our findings indicated that the removal effectiveness of BPA improved when PMS was introduced following the saturation adsorption of Fe@NC-KOH-x, as compared to the simultaneous introduction of Fe@NC-KOH-x and PMS. More particularly, through regression analysis, we found that the proportion of reactive species in the Fe@NC-KOH-x/PMS system changes with the increase of pyrolysis temperature, and there was a certain relationship between structure-function and active species in the Fe@NC-KOH-x/PMS system. O-C = O, Fe-N4, C-O, and pyrrolic N in Fe@NC-KOH-x lead to the generation of •OH, and SO4-•, C = O, Fe-N4, and defect are closely related to FeIV = O, and the formation of 1O2 is affected by Fe-N4, graphite N, C = O, and defect. Also, the density functional theory (DFT) calculation and the potential correlation between catalyst active centers and reactive oxygen species indicate that Fe-N4 is the main active site of Fe@NC-KOH-x. These outcomes of the study offer an innovation for enhanced elimination of BPA in wastewater treatment and provide a dynamic understanding of the mechanism of BPA degradation.

Interfacial SbOC bond and structural confinement synergistically boosting the reaction kinetics and reversibility of Sb2Se3/NC nanorods anode for sodium storage.

Antimony selenide (Sb2Se3) has been considered as a prospective material for sodium-ion batteries (SIBs) because of its large theoretical capacity. Whereas, grievous volume expansion caused by the conversion-alloying reaction leads to fast capacity decay and inferior cycle stability. Herein, the confined Sb2Se3 nanorods in nitrogen-doped carbon (Sb2Se3/NC) with interfacial chemical bond is designed to further enhance sodium storage properties of Sb2Se3. The robust enhancing effect of interfacial SbOC bonds can significantly promote electron transfer, Na+ ions diffusion kinetics and alloying reaction reversibility, combining the synergistic effect of the unique confinement structure of N-doped carbon shells can efficiently alleviate the volume change to ensure the structural integrity. Moreover, in-situ X-ray diffraction reveals intercalation/de-intercalation, conversion/reversed conversion reaction and alloying/de-alloying reaction mechanisms, and the kinetics analysis demonstrates the diffusion-controlled to contribute high capacity. As a result, Sb2Se3/NC anode delivers a high reversible capacity of 612.6 mAh/g at 0.1 A/g with a retentive specific capacity of 471.4 mAh/g after 1000 cycles, and long-cycle durability of over 2000 cycle with the reversible capacities of 371.1 and 297.3 mAh/g at 1 and 2 A/g are achieved, respectively, and an good rate capability. This distinctive interfacial chemical bonds and confinement effect design shows potential applications in the improved conversion/alloying-type materials for SIBs.

Non-criteria and criteria antiphospholipid antibodies and their association with pregnancy outcomes in women with a history of miscarriage: A retrospective study.

INTRODUCTION: The objective of this study was to investigate both antiphospholipid antibodies (aPLs) and non-criteria aPLs (NC-aPLs) in relation with pregnancy outcomes. METHODS: We retrospectively analyzed 1574 pregnant women with experienced at least one miscarriage who were tested for aPLs and NC-aPLs, and compared their clinical characteristics, immune biomarkers, and pregnancy outcomes. The χ2 test or Fisher's exact test compared pregnancy outcomes among patients negative for all aPLs, positive for NC­aPLs subtypes, and positive for criteria aPLs subtypes. RESULTS: Multivariate logistic regression analysis indicated that positive aPLs (OR = 2.216, 95 % CI 1.381-3.558), and positive NC-aPLs (OR = 1.619, 95 % CI 1.245-2.106) are linked to adverse outcomes. For fetal loss, positive aPLs (OR = 2.354, 95 % CI 1.448-3.829), NC-aPLs (OR = 1.443, 95 % CI 1.076-1.936) were significant. Premature delivery was associated with positive NC-aPLs (OR = 2.102, 95 % CI 1.452-3.043). In the NC-aPLs positive group, the rate of adverse outcomes was higher in the multiple-positive subgroup (77.8 %) compared to the double-positive (52.3 %) and single-positive (37.0 %) subgroups. The rates of fetal loss and premature delivery were also higher in the multiple-positive NC-aPLs subgroup compared to the single-positive subgroup (48.1 % vs. 22.6 % for fetal loss and 57.1 % vs. 16.5 % for premature delivery). DISCUSSION: Our findings suggest that both aPLs and NC-aPLs are associated with an increased incidence of adverse pregnancy outcomes, and patients presenting with multiple NC-aPLs positivity were found to have a higher incidence of adverse outcomes compared to their single-positive counterparts.

Mitigating Intraphase Catalytic-Domain Transfer via CO2 Laser for Enhanced Nitrate-to-Ammonia Electroconversion and Zn-Nitrate Battery Behavior.

Developing sustainable energy solutions is critical for addressing the dual challenges of energy demand and environmental impact. In this study, a zinc-nitrate (Zn-NO3 -) battery system was designed for the simultaneous production of ammonia (NH3) via the electrocatalytic NO3 - reduction reaction (NO3RR) and electricity generation. Continuous wave CO2 laser irradiation yielded precisely controlled CoFe2O4@nitrogen-doped carbon (CoFe2O4@NC) hollow nanocubes from CoFe Prussian blue analogs (CoFe-PBA) as the integral electrocatalyst for NO3RR in 1.0 M KOH, achieving a remarkable NH4 + production rate of 10.9 mg h-1 cm-2 at -0.47 V versus Reversible Hydrogen Electrode with exceptional stability. In situ and ex situ methods revealed that the CoFe2O4@NC surface transformed into high-valent Fe/CoOOH active species, optimizing the adsorption energy of NO3RR (*NO2 and *NO species) intermediates. Furthermore, density functional theory calculations validated the possible NO3RR pathway on CoFe2O4@NC starting with NO3 - conversion to *NO2 intermediates, followed by reduction to *NO. Subsequent protonation forms the *NH and *NH2 species, leading to NH3 formation via final protonation. The Zn-NO3 - battery utilizing the CoFe2O4@NC cathode exhibits dual functionality by generating electricity with a stable open-circuit voltage of 1.38 V versus Zn/Zn2+ and producing NH3. This study highlights the innovative use of CO2 laser irradiation to transform Prussian blue analogs into cost-effective catalysts with hierarchical structures for NO3RR-to-NH3 conversion, positioning the Zn-NO3 - battery as a promising technology for industrial applications.

Rational Construction of Honeycomb-like Carbon Network-Encapsulated MoSe2 Nanocrystals as Bifunctional Catalysts for Highly Efficient Water Splitting.

The scalable fabrication of cost-efficient bifunctional catalysts with enhanced hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) performance plays a significant role in overall water splitting in hydrogen production fields. MoSe2 is considered to be one of the most promising candidates because of its low cost and high catalytic activity. Herein, hierarchical nitrogen-doped carbon networks were constructed to enhance the catalytic activity of the MoSe2-based materials by scalable free-drying combined with an in situ selenization strategy. The rationally designed carbonaceous network-encapsulated MoSe2 composite (MoSe2/NC) endows a continuous honeycomb-like structure. When utilized as a bifunctional electrocatalyst for both HER and OER, the MoSe2/NC electrode exhibits excellent electrochemical performance. Significantly, the MoSe2/NC‖MoSe2/NC cells require a mere 1.5 V to reach a current density of 10 mA cm-2 for overall water splitting in 1 M KOH. Ex situ characterizations and electrochemical kinetic analysis reveal that the superior catalytic performance of the MoSe2/NC composite is mainly attributed to fast electron and ion transportation and good structural stability, which is derived from the abundant active sites and excellent structural flexibility of the honeycomb-like carbon network. This work offers a promising pathway to the scalable fabrication of advanced non-noble bifunctional electrodes for highly efficient hydrogen evolution.

Papain Suppresses Atopic Skin Inflammation through Anti-Inflammatory Activities Using In Vitro and In Vivo Models.

Papain (PN) is a proteolytic enzyme derived from Carica Papaya L. While the pharmacological effects of PN have not been extensively studied compared to its enzymatic activity, PN also holds potential benefits beyond protein digestion. This study aimed to investigate the potential effects of PN against skin inflammation in house dust mite Dermatophagoides farinae body (Dfb)-exposed NC/Nga atopic dermatitis (AD) mice and human HaCaT keratinocytes and their underlying mechanisms. The effects of PN on the skin were assessed via histological examination, measurements of transepidermal water loss (TEWL), quantitative reverse transcription-polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay. Our findings indicated that the oral intake of PN decreased the severity scores of lesions resembling AD, TEWL, and the levels of inflammatory cytokines and serum immunoglobulin E in Dfb-induced AD mice, along with a reduction in epidermal thickness and mast cell infiltration. Additionally, PN inhibited the activation of the mitogen-activated protein kinases (MAPKs) and the signal transducer and activator of transcription (STAT) pathways in Dfb-induced AD mice and HaCaT keratinocytes. Moreover, PN improved survival and reduced ROS production in H2O2-damaged HaCaT keratinocytes and enhanced the expression of antioxidant enzymes in Dfb-induced AD mice. Concludingly, the oral administration of PN suppressed inflammatory mediators and downregulated the MAPKs/STAT pathway, suggesting its potential role in AD pathogenesis.