In Situ Electrochemical Interfacial Polymerization for Covalent Organic Frameworks with Tunable Electrochromism.

A rapid in situ synthesis of electrochromic covalent organic frameworks (EC-COFs) was proposed by using green electrochemical interface polymerization of N,N,N',N'-tetrakis(p-aminophenyl)p-phenylenediamine (TPDA) and 2,5-dihydroxy-p-phenylenedicarboxaldehyde (DHBD). The synthetized TPDA-DHBD films exhibit stable polymorphic colour variations under different applied potentials, which can be attributed to the redox state changes of bis(triphenylamine) and imine electroactive functional groups within the COFs skeleton. TPDA-DHBD represents markedly different electrochromisms from red to cyan due to the steric hindrance effect caused by the presence of UO22+, demonstrating the unique tunability of COFs materials. This work offers a new feasible idea for rapid EC-COFs synthesis and tunable EC-COFs realization.

Screening of polyurethane-degrading microbes using a quenching fluorescence probe by microfluidic droplet sorting.

Excessive use of polyurethane (PU) polymers has led contributed to serious environmental pollution. The plastic recycling technology using microorganisms and enzymes as catalysts offers a promising green and low-carbon approach for managing plastic waste. However, current methods for screening PU-degrading strains suffer from drawbacks such as being time-consuming and inefficient. Herein, we present a novel approach for screening PU-degrading microorganisms using a quenching fluorescent probe along with the fluorescence-activated droplet sorting (FADS). The FPAP could specifically recognize the 4,4'-methylenedianiline (MDA) derivates released from PU degradation, with fluorescence quenching as a response. Based on the approach, we successfully screen two PU-degrading strains (Burkholderia sp. W38 and Bacillus sp. C1). After 20 d of cultivation, strain W38 and C1 could degrade 41.58% and 31.45% of polyester-PU film, respectively. Additionally, three metabolites were identified during the degradation of PU monomer (2,4-toluene diamine, 2,4-TDA) and a proposed degradation pathway was established. Consequently, the fluorescence probe integrated with microfluidic droplet systems, demonstrates potential for the development of innovative PU-biocatalysts. Furthermore, the identification of the 2,4-TDA degradation pathway provides valuable insights that can propel advancements in the field of PU biodegradation.

Influence of non-pharmaceutical interventions on epidemiological characteristics of Mycoplasma pneumoniae infection in children during and after the COVID-19 epidemic in Ningbo, China.

Background: Since the outbreak of COVID-19, China has implemented a series of non-pharmaceutical interventions (NPIs), effectively containing the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as various respiratory pathogens. With the continuous relaxation of restrictions, China has entered a new phase of the post-pandemic era. However, the epidemiological differences of Mycoplasma pneumoniae (MP) between the two phases in Ningbo and even in China remain unclear. Methods: Data of children aged 0-14 years who visited the Ningbo Medical Center LiHuiLi Hospital due to acute respiratory tract infections from January 2020 to December 2023 were collected. PCR was used to detect 13 respiratory pathogens and the macrolide-resistance of Mycoplasma pneumoniae. Results: Among 10,206 children, 2,360 were infected with MP (23.12%). Among the total, the MP positive rate during the NPI phase (6.35%) was significantly lower than that during the non-NPI phase (34.28%), while the macrolide resistance rate increased from 62.5% (NPI phase) to 81.1% (non-NPI phase). The rate of MP co-infection increased from 11.2% (NPI phase) to 30.3% (non-NPI phase). MP infection exhibited obvious seasonality, with the highest prevalence in autumn (30.0%) followed by summer (23.6%). There were differences in MP positivity rates among different age groups, with the highest among school-age children at 39.5%. During the NPI phase, all age groups were less susceptible to MP, while during the non-NPI phase, the susceptible age for MP was 4-12 years, with 8 years being the most susceptible. The susceptible age for MP co-infection was 0-6 years. MP exhibited antagonistic effects against numerous pathogens. Compared to MP single infection, the proportion of pneumonia was higher in MP co-infection cases. Conclusion: The removal of NPIs significantly impacted the spread of MP, altering population characteristics including age, seasonality, macrolide resistance, and MP co-infection rates.

Molecular Editing of Ketones through N-Heterocyclic Carbene and Photo Dual Catalysis.

The molecular editing of ketones represents an appealing strategy due to its ability to maximize the structural diversity of ketone compounds in a straightforward manner. However, developing efficient methods for the arbitrary modification of ketonic molecules, particularly those integrated within complex skeletons, remains a significant challenge. Herein, we present a unique strategy for ketone recasting that involves radical acylation of pre-functionalized ketones facilitated by N-heterocyclic carbene and photo dual catalysis. This protocol features excellent substrate tolerance and can be applied to the convergent synthesis and late-stage functionalization of structurally complex bioactive ketones. Mechanistic investigations, including experimental studies and density functional theory (DFT) calculations, shed light on the reaction mechanism and elucidate the basis of the regioselectivity.

Rapid and extensive SARS-CoV-2 Omicron variant infection wave revealed by wastewater surveillance in Shenzhen following the lifting of a strict COVID-19 strategy.

Wastewater-based epidemiology (WBE) has emerged as a promising tool for monitoring the spread of COVID-19, as SARS-CoV-2 can be shed in the faeces of infected individuals, even in the absence of symptoms. This study aimed to optimize a prediction model for estimating COVID-19 infection rates based on SARS-CoV-2 RNA concentrations in wastewater, and reveal the infection trends and variant diversification in Shenzhen, China following the lifting of a strict COVID-19 strategy. Faecal samples (n = 4337) from 1204 SARS-CoV-2 infected individuals hospitalized in a designated hospital were analysed to obtain Omicron variant-specific faecal shedding dynamics. Wastewater samples from 6 wastewater treatment plants (WWTPs) and 9 pump stations, covering 3.55 million people, were monitored for SARS-CoV-2 RNA concentrations and variant abundance. We found that the viral load in wastewater increased rapidly in December 2022 in the two districts, demonstrating a sharp peak in COVID-19 infections in late-December 2022, mainly caused by Omicron subvariants BA.5.2.48 and BF.7.14. The prediction model, based on the mass balance between total viral load in wastewater and individual faecal viral shedding, revealed a surge in the cumulative infection rate from <0.1 % to over 70 % within three weeks after the strict COVID-19 strategy was lifted. Additionally, 39 cryptic SARS-CoV-2 variants were identified in wastewater, in addition to those detected through clinical surveillance. These findings demonstrate the effectiveness of WBE in providing comprehensive and efficient assessments of COVID-19 infection rates and identifying cryptic variants, highlighting its potential for monitoring emerging pathogens with faecal shedding.

Biodetoxification of Lignocellulose Hydrolysate for Direct Use in Succinic Acid Production.

The pretreatment of lignocellulosic biomass with acid generates phenolic and furanyl compounds that function as toxins by inhibiting microbial growth and metabolism. Therefore, it is necessary to detoxify acid-pretreated lignocellulosic biomass for better utilization. Among the various detoxification methods that are available, biodetoxification offers advantages that include mild reaction conditions and low energy consumption. In this study, a newly isolated Rhodococcus aetherivorans strain, N1, was found to effectively degrade various lignin-derived aromatic compounds, such as p-coumarate, ferulate, syringaldehyde, furfural, and 5-hydroxymethylfurfural. Furthermore, the metabolic pathway and genes responsible for this degradation were also identified. In addition, the overexpression of a demethylase (DesA) and 3,4-dioxygenase (DesZ) in strain N1 generated a recombinant strain, N1-S, which showed an enhanced ability to degrade syringaldehyde and 80.5% furfural, 50.7% 5-hydroxymethylfurfural, and 71.5% phenolic compounds in corn cob hydrolysate. The resulting detoxified hydrolysate was used directly as a feedstock for succinate production by Escherichia coli suc260. This afforded 35.3 g/l succinate, which was 6.5 times greater than the concentration afforded when nondetoxified hydrolysate was used. Overall, the results of this study demonstrate that strain N1-S is a valuable microbe for the biodetoxification of lignocellulosic biomass.

High-Performance Suspension Bead Sensor Based on Optical Tweezers and Immuno-Rolling Circle Amplification.

In recent years, optical tweezers have become an effective bioassay tool due to their unique advantages, especially in combination with suspension beads, which can be applied to develop a high-performance analysis platform capable of high-quality imaging and stable signal output. However, the optical tweezer-assisted bead analysis is still at the early stage, and further development of different favorable methods is in need. Herein, we have first developed the optical tweezer-assisted immuno-rolling circle amplification (immuno-RCA) on beads for protein detection. Prostate-specific antigen was selected as the model analyte, and the immunosandwich structure on beads was built by the high affinity of "antibody-antigen". The "protein-nucleic acid" signals were effectively converted through the covalent coupling procedure of antibodies and oligonucleotides, further initiating the RCA reaction to achieve signal amplification. The individual beads with the strong irregular Brownian motion in a fluid environment were eventually trapped by the optical tweezers to acquire the accurate and high-quality signal. Compared with the conventional immunoassay on beads, the sensitivity of the developed strategy was increased by 587 times with a limit of detection of 4.29 pg/mL (0.13 pM), as well as excellent specificity, stability, and reproducibility. This study developed the new optical tweezer-assisted beads imaging strategy for protein targets, which has great potential for being applied to clinical serology research and expands the application of optical tweezers in the bioassays.

Assessment of epidemic risk state and its change trend of public hospital in underdeveloped area in different stages.

Objective: Epidemics are sudden and rapidly spreading. Hospitals in underdeveloped areas are particularly vulnerable in case of an outbreak. This paper aims to assess the epidemic risk state and its change trend of hospitals in different epidemic stages, identify the key factors affecting hospital epidemic risk change, provide priority reference for hospital epidemic risk control, and enhance the hospital's ability to respond to sudden epidemics. Methods: Based on Grounded theory, the epidemic risk indicators that affect hospital safety are summarized. The concept of epidemic risk state and its random state space is proposed according to Markov chain theory. The impact of each indicator on the random risk state and its change is comprehensively assessed from two aspects: risk occurrence probability and risk loss. Finally, the assessment of the hospital epidemic risk state and its change at different stages is achieved. Results: The stable risk states of public hospitals in underdeveloped areas in non-epidemic stage t0, early epidemic stage t1, and outbreak stage t2 are P ^ t 0 ( S n ) = { 0 . 142 , 0 . 546 , 0 . 220 , 0 . 093 } , P ^ t 1 ( S n ) = { 0 . 025 , 0 . 364 , 0 . 254 , 0 . 357 } , and P ^ t 2 ( S n ) = { 0 . 020 , 0 . 241 , 0 . 191 , 0 . 548 } , respectively. In non-epidemic stage, the key factor in improving the hospital epidemic risk state is emergency funding. In early epidemic stage, the key factors in improving the hospital epidemic risk state are the training of medical staff in epidemic prevention skills and the management of public health. In outbreak state, the key factor in improving the hospital epidemic risk state is the training of medical staff in epidemic prevention skills and psychological awareness. Conclusion: This paper proposes the concept of epidemic risk state, providing an effective assessment method for the epidemic risk state and its change trend in public hospitals. According to the assessment, public hospitals in underdeveloped areas in different epidemic stages should adopt different risk control strategies to improve their current risk state. Blind risk control is inefficient and may even cause the epidemic risk to transition toward a more dangerous state.

Photobiomodulation Using 830 nm Lighting-Emitting Diode Inhibits Melanogenesis via FOXO3a in Human Melanocyte.

Photobiomodulation (PBM) using 830 nm light-emitting diode (LED) benefits tissue regeneration, wound healing and neural stimulation. However, there is not much exploration of its effect on melanocytes and ex vivo skin model. This study aims to investigate the mechanism behind the anti-melanogenic activity of 830 nm LED and provides evidence for its activity in human ex vivo skin model. Our results showed that 830 nm LED at fluences ranging from 5 to 20 J/cm2 inhibited melanosome maturation and reduced melanin content, tyrosinase activity and melanogenesis-related proteins. 830 nm LED inhibited the phosphorylation of AKT and its downstream FOXO3a, leading to nuclear translocation of FOXO3a. Furthermore, FOXO3a knockdown and AKT activator like SC79 could reverse the melanogenesis inhibition phenotype induced by 830 nm LED. In human ex vivo skin model, Fontana-Masson staining revealed a decrease in epidermal basal pigmentation after 830 nm LED irradiation. Taken together, 830 nm LED demonstrated the anti-melanogenic activity via FOXO3a.

Rapid and specific differentiation of Salmonella enterica serotypes typhi and Paratyphi by multicolor melting curve analysis.

Rapid and accurate identification of Salmonella enterica serotypes Typhi and Paratyphi (A, B and C), the causal agents of enteric fever, is critical for timely treatment, case management and evaluation of health policies in low and middle-income countries where the disease still remains a serious public health problem. The present study describes the development of a multiplex assay (EFMAtyping) for simultaneous identification of pathogens causing typhoid and paratyphoid fever in a single reaction by the MeltArray approach, which could be finished within 2.5 h. Seven specific genes were chosen for differentiation of typhoidal and nontyphoidal Salmonella. All gene targets were able to be detected by the EFMAtyping assay, with expected Tm values and without cross-reactivity to other relevant Salmonella serovars. The limit of detection (LOD) for all gene targets was 50 copies per reaction. The LOD reached 102-103 CFU/ml for each pathogen in simulated clinical samples. The largest standard deviation value for mean Tm was below 0.5 °C. This newly developed EFMAtyping assay was further evaluated by testing 551 clinical Salmonella isolates, corroborated in parallel by the traditional Salmonella identification workflow, and serotype prediction was enabled by whole-genome sequencing. Compared to the traditional method, our results exhibited 100% of specificity and greater than 96% of sensitivity with a kappa correlation ranging from 0.96 to 1.00. Thus, the EFMAtyping assay provides a rapid, high throughput, and promising tool for public health laboratories to monitor typhoid and paratyphoid fever.

Microbial biofilms as a platform for diverse biocatalytic applications.

Microbial biofilms have gained significant traction in commercial wastewater treatment due to their inherent resilience, well-organized structure, and potential for collaborative metabolic processes. As our understanding of their physiology deepens, these living catalysts are finding exciting applications beyond wastewater treatment, including the production of bulk and fine chemicals, bioelectricity generation, and enzyme immobilization. While the biological applications of biofilms in different biocatalytic systems have been extensively summarized, the applications of artificially engineered biofilms were rarely discussed. This review aims to bridge this gap by highlighting the untapped potential of engineered microbial biofilms in diverse biocatalytic applications, with a focus on strategies for biofilms engineering. Strategies for engineering biofilm-based systems will be explored, including genetic modification, synthetic biology approaches, and targeted manipulation of biofilm formation processes. Finally, the review will address key challenges and future directions in developing robust biofilm-based biocatalytic platforms for large-scale production of chemicals, pharmaceuticals, and biofuels.

Phillyrin and its metabolites exert antipyretic effects by targeting the NAD+ binding domain of GAPDH, MDH2 and IDH2.

BACKGROUND: Fever is one of the main pathophysiological reactions that occurs during the acute phase of various diseases. Excessive body temperature can lead to various adverse consequences such as brain tissue damage and abnormal immune responses. Phillyrin (Phr) is the main active ingredient in Forsythia suspensa (Thunb.) Vahl (Lian Qiao) and has antipyretic effects; however, its antipyretic mechanism of action remains unclear. PURPOSE: This study aimed to explore the antipyretic mechanisms of Phr and provide a new treatment plan for fever. METHODS: The antipyretic effects of Phr were evaluated using a mouse model of pneumonia fever. The main metabolites of Phr involved in its antipyretic function were identified using a mitochondrial temperature-sensitive probe. Further synthesis of the main metabolite, phillygenin (Phg), an alkynylated probe, was performed, and chemical proteomics was used to capture and analyze its direct target for antipyretic effects. The mechanism of action of Phg and its antipyretic targets was explored using metabolomics and various molecular biology methods. RESULTS: Phr showed significant antipyretic and anti-inflammatory effects in a mouse model of lipopolysaccharide-induced fever. Phg reversibly targeted the nicotinamide adenine dinucleotide (NAD+) binding domain of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), malate dehydrogenase 2 (MDH2), and isocitrate dehydrogenase 2 (IDH2) to inhibit their enzymatic activity. In-depth analysis of cellular metabolomics and mitochondrial stress testing indicated that inhibition of GAPDH, MDH2, and IDH2 enzyme activity by Phg led to a decrease in cellular energy supply and heat production regulated by glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation signaling pathways. Phg specifically targeted macrophages and inhibited LPS-induced macrophage activation by downregulating GAPDH enzyme activity, thereby exerting anti-inflammatory effects. In vivo experiments also confirmed that the antipyretic effect of Phr in LPS-induced fever model mice was related to its main metabolites, Phg and Phg-sulfonate (Phg-S), which directly targeted the NAD+ binding domain of GAPDH, IDH2, and MDH2, inhibiting the activity of these enzymes, thereby reducing energy supply and regulating febrile-related inflammatory factors. CONCLUSION: This study reported for the first time that the antipyretic effect of Phr is produced by targeting GAPDH, IDH2, and MDH2 to regulate energy supply and febrile-related inflammatory factors through its main metabolites Phg and Phg-S. This study not only provides potential drugs for fever treatment but also provides new ideas for improving clinical fever treatment plans.

Rapidly progressive necrotizing enterocolitis: Risk factors and a predictive model.

BACKGROUND: Rapidly progressive necrotizing enterocolitis (RP-NEC) is a particular subtype of NEC known for its rapid progression and high mortality rate. The objective of this study was to establish a predictive model for RP-NEC. METHODS: This was a retrospective single-center cohort study. Patients were newborn infants with NEC (Bell's stage ≥ IIB) admitted from January 1, 2016 to December 31, 2023. The primary outcome was RP-NEC defined as the need for surgical intervention and/or death within 48 hours of the onset of NEC. RESULTS: Totally 334 newborn infants were included, among which 82 (24.6%) were RP-NEC cases with a gestation age 34.1 (31.0, 37.0) weeks and birth weight 2100 (1413, 2800) g. Plasma sodium <135 mmol/L, C-reactive protein ≥10 mg/L, platelet count <100 × 109/L, lymphocyte count <1.5 × 109/L, pH <7.2 in blood gas, and ascites at NEC onset were identified as independent risk factors for RP-NEC. The model established presented an AUC value of 0.983 (95% CI 0.97-0.99). The calibration curve for validation was applied revealing a slope close to unity while the Hosmer-Lemeshow test yielded χ2 = 2.550 (p = 0.636). CONCLUSION: The predictive model established on the above 6 items of RP-NEC is highly promising. IMPACT: Currently, there is a paucity of research on this specific type of severe necrotizing enterocolitis (NEC) characterized by rapid progression. Our study was to investigate the risk factors associated with surgical intervention and/or death within 48 hours following onset in infants with NEC, establish a predictive model for infants with rapidly progressive NEC. The new data presented in this study was the ROC curve combining the above factors as well as hyponatremia.

Effects of busy mindset on preference for high-calorie foods.

More people feel busier than ever. Recognising busyness as an environmental factor that influences food preferences is essential when considering health-related decisions. This research investigates how the subjective perception of busyness-which is referred to as a busy mindset-affects consumers' food preferences via two studies. Study 1 was a laboratory experiment conducted using a manipulation method with 135 undergraduate student participants. Study 2 used an online self-report questionnaire to repeat the findings of Study 1 and including 209 social participants. The results from the two studies showed that a busy mindset induced individuals to prefer high-calorie foods, and energy expenditure efficiency mediated this effect. Moreover, the subjective perception of busyness increased individuals' estimated need for calories and induced them to prefer high-calorie foods over high-nutrition or hedonic foods. These findings suggest that food preferences in the busy mindset have potential implications for individuals' food consumption.

Maternal age enhances purifying selection on pathogenic mutations in complex I genes of mammalian mtDNA.

Mitochondrial diseases, caused mainly by pathogenic mitochondrial DNA (mtDNA) mutations, pose major challenges due to the lack of effective treatments. Investigating the patterns of maternal transmission of mitochondrial diseases could pave the way for preventive approaches. In this study, we used DddA-derived cytosine base editors (DdCBEs) to generate two mouse models, each haboring a single pathogenic mutation in complex I genes (ND1 and ND5), replicating those found in human patients. Our findings revealed that both mutations are under strong purifying selection during maternal transmission and occur predominantly during postnatal oocyte maturation, with increased protein synthesis playing a vital role. Interestingly, we discovered that maternal age intensifies the purifying selection, suggesting that older maternal age may offer a protective effect against the transmission of deleterious mtDNA mutations, contradicting the conventional notion that maternal age correlates with increased transmitted mtDNA mutations. As collecting comprehensive clinical data is needed to understand the relationship between maternal age and transmission patterns in humans, our findings may have profound implications for reproductive counseling of mitochondrial diseases, especially those involving complex I gene mutations.

New Classes of Magnetic Noise Self-Compensation Effects in Atomic Comagnetometer.

Precision measurements of anomalous spin-dependent interactions are often hindered by magnetic noise and other magnetic systematic effects. Atomic comagnetometers use the distinct spin precession of two species and have emerged as important tools for effectively mitigating the magnetic noise. Nevertheless, the operation of existing comagnetometers is limited to very low-frequency noise commonly below 1 Hz. Here, we report a new type of atomic comagnetometer based on a magnetic noise self-compensation mechanism originating from the destructive interference between alkali-metal and noble-gas spins. Our comagnetometer employing K-^{3}He system remarkably suppresses magnetic noise exceeding 2 orders of magnitude at higher frequencies up to 160 Hz. Moreover, we discover that the capability of our comagnetometer to suppress magnetic noise is spatially dependent on the orientation of the noise and can be conveniently controlled by adjusting the applied bias magnetic field. Our findings open up new possibilities for precision measurements, including enhancing the search sensitivity of spin-dark matter particles interactions into unexplored parameter space.

A General Copper-Box System for the Asymmetric Arylative Functionalization of Benzylic, Propargylic or Allenylic Radicals.

Radical-involved arylative cross-coupling reactions have recently emerged as an attractive strategy to access valuable aryl-substituted motifs. However, there still exist several challenges such as limited scope of radical precursors/acceptors, and lack of general asymmetric catalytic systems, especially regarding the multicomponent variants. Herein, we reported a general copper-Box system for asymmetric three-component arylative radical cross-coupling of vinylarenes and 1,3-enynes, with oxime carbonates and aryl boronic acids. The reactions proceed under practical conditions in the absence or presence of visible-light irradiation, affording chiral 1,1-diarylalkanes, benzylic alkynes and allenes with good enantioselectivities. Mechanistic studies imply that the copper/Box complexes play a dual role in both radical generation and ensuing asymmetric cross-coupling. In the cases of 1,3-enynes, visible-light irradiation could improve the activity of copper/Box complex toward the initial radical generation, enabling better efficiency match between radical formation and cross-coupling.

Tetrandrine inhibits aldosterone synthesis by covalently targeting CYP11A1 to attenuate hypertension.

Introduction: Tetrandrine (Tet) is the main pharmacological component of Stephania tetrandra S. Moore, which is a well-documented traditional Chinese medicine known for its diuretic and antihypertensive properties. Unraveling the specific targets and mechanisms of Tet involved in inducing diuresis and mitigating hypertension can provide valuable insights into its therapeutic effects. This study aimed to explore the diuretic and antihypertensive targets and mechanisms of Tet using chemical biology coupled with activity analyses in vivo and in vitro. Methods: The diuretic effects of Tet were evaluated using a water-loaded mouse model. The direct target proteins for the diuretic and antihypertensive effects of Tet were determined using chemical biology. Furthermore, the molecular mechanism of Tet binding to target proteins was analyzed using a multidisciplinary approach based on the structure and function of the proteins. Finally, the effects of the Tet-targeted protein on downstream signaling pathways and blood pressure were evaluated in hypertensive model rats. Results: Tet exhibited significant antihypertensive and potassium-preserving diuretic effects. The mechanism underlying these effects involves the modulation of the enzyme activity by covalent binding of Tet to Cys423 of CYP11A1. This interaction alters the stability of heme within CYP11A1, subsequently impeding electron transfer and inhibiting aldosterone biosynthesis. Discussion: This study not only revealed the mechanism of the diuretic and antihypertensive effects of Tet but also discovered a novel covalent inhibitor of CYP11A1. These findings contribute significantly to our understanding of the therapeutic potential of Tet and provide a foundation for future research in the development of targeted treatments for hypertension.