External fields effectively switch the spin channels of transition metal-doped ß-phase tellurene from first principles.

Non-volatile magnetic random-access memories have proposed the need for spin channel switching. However, this presents a challenge as each spin channel reacts differently to the external field. Tellurene is a semiconductor with a tunable bandgap, excellent stability, and high carrier concentration, but its lack of magnetic properties has hindered its application in spintronics. In this work, the influence of an external field on transition metal (TM)-doped ß-tellurene is systematically analysed from first principles. First, the active-learning moment-tensor-potential (MTP) is used to verify the thermal stability of the V-doped system with the MTP proving to be 900 times faster than the traditional method. Subsequently, under biaxial strain ranging from -2% to 10%, the V-doped system undergoes a gradual transition from a magnetic semiconductor to a spin-gapless semiconductor, and further to a half-metal and magnetic metal. The band structure can be maintained under an electric field. By examining the magnetic anisotropy energy, the lattice changes profoundly impact the electromagnetic properties, particularly with the TMs being sensitive to strain. Moreover, the band structure is reflected in the spin resolution current of the magnetic tunnel junction. This work investigates the response of doped ß-Te to external fields, revealing its potential applications in spintronics.

Reducing postoperative hypothermia in infants: Quality improvement in China.

BACKGROUND: Unintended postoperative hypothermia in infants is associated with increased mortality and morbidity. We noted consistent hypothermia postoperatively in more than 60% of our neonatal intensive care (NICU) babies. Therefore, we set out to determine whether a targeted quality improvement (QI) project could decrease postoperative hypothermia rates in infants. OBJECTIVES: Our SMART aim was to reduce postoperative hypothermia (<36.5°C) in infants from 60% to 40% within 6 months. METHODS: This project was approved by IRB at Guangzhou Women and Children's Medical Center, China. The QI team included multidisciplinary healthcare providers in China and QI experts from Children's Hospital of Philadelphia, USA. The plan-do-study-act (PDSA) cycles included establishing a perioperative-thermoregulation protocol, optimizing the transfer process, and staff education. The primary outcome and balancing measures were, respectively, postoperative hypothermia and hyperthermia (axillary temperature < 36.5°C, >37.5°C). Data collected was analyzed using control charts. The factors associated with a reduction in hypothermia were explored using regression analysis. RESULTS: There were 295 infants in the project. The percentage of postoperative hypothermia decreased from 60% to 37% over 26 weeks, a special cause variation below the mean on the statistical process control chart. Reduction in hypothermia was associated with an odds of 0.17 (95% CI: 0.06-0.46; p <.001) for compliance with the transport incubator and 0.24 (95% CI: 0.1-0.58; p =.002) for prewarming the OR ambient temperature to 26°C. Two infants had hyperthermia. CONCLUSIONS: Our QI project reduced postoperative hypothermia without incurring hyperthermia through multidisciplinary team collaboration with the guidance of QI experts from the USA.

Comparative genomics provides insights into the aquatic adaptations of mammals.

The ancestors of marine mammals once roamed the land and independently committed to an aquatic lifestyle. These macroevolutionary transitions have intrigued scientists for centuries. Here, we generated high-quality genome assemblies of 17 marine mammals (11 cetaceans and six pinnipeds), including eight assemblies at the chromosome level. Incorporating previously published data, we reconstructed the marine mammal phylogeny and population histories and identified numerous idiosyncratic and convergent genomic variations that possibly contributed to the transition from land to water in marine mammal lineages. Genes associated with the formation of blubber (NFIA), vascular development (SEMA3E), and heat production by brown adipose tissue (UCP1) had unique changes that may contribute to marine mammal thermoregulation. We also observed many lineage-specific changes in the marine mammals, including genes associated with deep diving and navigation. Our study advances understanding of the timing, pattern, and molecular changes associated with the evolution of mammalian lineages adapting to aquatic life.

Immunological assessment of a patient with Omenn syndrome resulting from compound heterozygous mutations in the RAG1 gene.

The recombination activating gene 1 (RAG1) is essential for V(D)J recombination during T- and B-cell development. In this study, we presented a case study of a 41-day-old female infant who exhibited symptoms of generalized erythroderma, lymphadenopathy, hepatosplenomegaly, and recurrent infections including suppurative meningitis and septicemia. The patient showed a T+B-NK+ immunophenotype. We observed an impaired thymic output, as indicated by reduced levels of naive T cells and sjTRECs, coupled with a restricted TCR repertoire. Additionally, T-cell CFSE proliferation was impaired, indicating a suboptimal T-cell response. Notably, our data further revealed that T cells were in an activated state. Genetic analysis revealed a previously reported compound heterozygous mutation (c. 1186C > T, p. R396C; c. 1210C > T, p. R404W) in the RAG1 gene. Structural analysis of RAG1 suggested that the R396C mutation might lead to the loss of hydrogen bonds with neighboring amino acids. These findings contribute to our understanding of RAG1 deficiency and may have implications for the development of novel therapies for patients with this condition.

An All-in-One "4A Hydrogel": through First-Aid Hemostatic, Antibacterial, Antioxidant, and Angiogenic to Promoting Infected Wound Healing.

Currently used wound dressings are ineffective. Hence, there is a need to develop introduce a high-performance medicament with multiple functions including rapid hemostasis and excellent antibacterial activity to meet the growing worldwide demand for wound healing products. Here, inspired by the strong adhesion of mussels and the enzyme-mimicking activity of nanometallic biomaterials, the authors developed an injectable hydrogel to overcome multiple limitations of current wound dressings. The hydrogel is synthesized via esterification reaction between poly(vinyl alcohol) (PVA) and 3,4-dihydroxyphenylalanine (DOPA), followed by catechol-metal coordination between Cu2+ and the catechol groups of DOPA to form a PVA-DOPA-Cu (PDPC) hydrogel. The PDPC hydrogel possesses excellent tissue adhesive, antioxidative, photothermal, antibacterial, and hemostatic properties. The hydrogel rapidly and efficiently stopped bleeding under different traumatic conditions, including otherwise-lethal liver injury, high-pressure carotid artery rupture, and even fatal cardiac penetration injuries in animal models. Furthermore, it is demonstrated that the PDPC hydrogel affected high-performance wound repair and tissue regeneration by accelerating re-epithelialization, promoting collagen deposition, regulating inflammation, and contributing to vascularization. The results show that PDPC hydrogel is a promising candidate for rapid hemorrhage control and efficient wound healing in multiple clinical applications.

Green infrastructure optimization considering spatial functional zoning in urban stormwater management.

Green infrastructure (GI) is used as an alternative and complement to traditional urban drainage system for mitigating urban stormwater issues mainly caused by climate change and urbanization. The combination of hydrological model and optimization algorithm can automatically find the optimal solution under multiple objectives. Given the multi-functional characteristics of GI, choosing the optimization objectives of GI are critical for multiple stakeholders. This study proposes a GI optimization method considering spatial functional zoning. Based on the basic conditions, the study area is divided into the flood risk control zone (FRCZ) and the total runoff control zone (TRCZ). The integrated model coupling hydrological model and optimization algorithm is applied to obtain the Pareto fronts and corresponding non-dominated solutions. The Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) method is used to support the decision-making process. The optimal solution obtained for the FRCZ achieves a flood risk reduction rate of 60.49% with an average life cycle cost per year of 0.20 × 108 Chinese Yuan (CNY); The optimal solution obtained for the TRCZ achieves a total runoff reduction rate of 22.83% with an average life cycle cost per year of 0.17 × 108 CNY. This study provides a reference for stakeholders in GI planning and design.

Passively mode-locked red Pr:LiYF4 laser based on a two-dimensional palladium diselenide saturable absorber.

We report a passively mode-locked Pr:LiYF4 (Pr:YLF) visible laser using a palladium diselenide (PdSe2) as a saturable absorber (SA) for the first time, to the best of our knowledge. The nonlinear optical properties of two-dimensional (2D) PdSe2 nanosheets in the visible band were studied by the open-aperture Z-scan technique. The results indicate the significant saturable absorption properties of PdSe2 nanosheets in the visible region. Furthermore, the continuous wave mode-locked (CWML) visible laser based on PdSe2 SA was successfully realized. Ultrashort pulses as short as 35 ps were obtained at 639.5 nm with a repetition rate of 80.3 MHz and a maximum output power of 116 mW. The corresponding pulse energy was 1.44 nJ and peak power was 41.3 W. These results indicate that 2D PdSe2 SA is a promising high stability passively mode-locked device for ultrafast solid-state visible lasers.

Direct generation of continuous-wave and passively Q-switched visible vortex beams from a doughnut-shaped diode-pumped Pr: YLF laser.

We demonstrate the direct generation of visible vortex beams (LG01 mode) from a doughnut-shaped diode-pumped Pr:YLF laser. In continuous-wave mode, the maximum vortex output power was 36 mW at 523 nm, 354 mW at 607 nm, 838 mW at 639 nm, 722 mW at 721 nm, respectively. Moreover, based on this operation, the orange and red passively Q-switched vortex lasers were also achieved by inserting a Co:MgAl2O4 crystal into the laser cavity as a saturable absorber. The shortest pulse width of Q-switched vortex laser was 58 ns for 607 nm, and 34 ns for 639 nm, respectively. Our work provides a reliable and efficient method for the direct generation of visible vortex lasers for potential applications.

A Piezo-Fenton System with Rapid Iron Cycling and Hydrogen Peroxide Self-Supply Driven by Ultrasound.

The piezo-Fenton system has attracted attention not only because it can enhance the Fenton reaction activity by mechanical energy input, but also because it is expected to realize a class of stimuli-responsive advanced oxidation systems by regulating energy input and hydrogen peroxide self-supply, thus greatly enriching the application possibilities of Fenton chemistry. In this work, a series of Fe-doped g-C3 N4 (g-C3 N4 -Fe) as a piezo-Fenton system were synthesized where the iron stably immobilized through Fe-N interaction. The piezo-induced electrons generate on g-C3 N4 matrix support the conversion of Fe(III) to Fe(II) and promote rate-limiting step of Fenton reaction. With the optimal Fe loading, g-C3 N4 -0.5Fe can achieve methylene blue (MB) degradation under ultrasonic treatment with first-order kinetic rate constants of 75×10-3  min-1 . Most importantly, the g-C3 N4 -Fe can maintain good catalytic activity in a wide pH range (pH=2.0∼9.0) and be cyclic used without iron leaching to solution (<0.001 µg ⋅ L-1 ), overcoming the disadvantage of traditional Fe-based Fenton catalysts that can only be applied under acidic conditions and prone to secondary pollution. In addition, g-C3 N4 -0.5Fe also exhibits antibacterial properties of Escherichia coli and Staphylococcus aureus under ultrasound. Hydroxyl radicals mainly contribute to the degradation of MB and the sterilization process. Our work is an attempt to clarify the role of g-C3 N4 -Fe in the conversion of mechanical energy to ROS and provide inspirations for the piezo-Fenton system design.

Potassium ferricyanide oxidizes silicon quantum dots under alkaline conditions to produce chemiluminescence for uric acid detection in human urine.

Potassium ferricyanide (K3 (Fe(CN)6 )) could directly oxidize silicon quantum dots (Si QDs) to generate chemiluminescence (CL) under alkaline conditions. It was noteworthy that in the Si QDs-K3 (Fe(CN)6 )-NaOH CL system, the Si QDs worked as a new luminescent material. In addition, the signal intensity of this CL system could be weakened with the addition of uric acid (UA). Based on these, we exploited a new easy and convenient determination method of UA. This method only needed filtration and dilution of UA, without other pretreatment. The constructed system exhibited a linear relationship that ranged from 0.50 to 4.50 mmol·L-1 , with 0.24 mmol·L-1 of detection limit, and this system had successfully demonstrated the detection of UA in human urine. In addition, this work also broaden the application of the Si QDs in CL research.

Circ_0027599 elevates RUNX1 expression via sponging miR-21-5p on gastric cancer progression.

BACKGROUND: Increasing evidence has shown that circular RNAs (circRNAs) serve as vital regulators in tumour progression. In this study, we focused on the functions of circ_0027599 in gastric cancer (GC) progression. METHODS: The levels of circ_0027599, runt-related transcription factor 1 (RUNX1) mRNA and microRNA-21-5p (miR-21-5p) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay. The protein levels of RUNX1, E-Cadherin, vimentin and N-Cadherin were measured by Western blot assay. Cell viability, colony formation, metastasis and cell cycle process were evaluated by Cell Counting Kit-8 (CCK-8) assay, colony formation assay, transwell assay and flow cytometry analysis, respectively. The interaction between circ_0027599 and miR-21-5p and the interaction between miR-21-5p and RUNX1 were verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The role of circ_0027599 in tumour growth in vivo was investigated by murine xenograft model assay. RESULTS: Circ_0027599 and RUNX1 were downregulated in GC tissues and cells. Circ_0027599 level was associated with the overall survival of GC patients. Circ_0027599 or RUNX1 overexpression inhibited GC cell viability, colony formation, migration, invasion and cell cycle process in vitro. For mechanism analysis, circ_0027599 positively regulated RUNX1 expression via functioning as the sponge for miR-21-5p. RUNX1 inhibition reversed circ_0027599 overexpression mediated malignant behaviours of GC cells. Moreover, circ_0027599 overexpression repressed tumour growth in vivo. CONCLUSION: Circ_0027599 overexpression repressed GC progression via modulation of miR-21-5p/RUNX1 axis, which might illumine a novel therapeutic target for GC.

Sleep of preschoolers during the coronavirus disease 2019 (COVID-19) outbreak.

Coronavirus disease 2019 (COVID-19) has resulted in a significantly large number of psychological consequences, including sleep health. The present study evaluated sleep patterns, sleep disturbances, and associated factors in Chinese preschoolers confined at home during the COVID-19 outbreak. Caregivers of 1619 preschoolers (aged 4-6 years) recruited from 11 preschools in Zunyi, Guizhou province completed the Children's Sleep Habit Questionnaire (CSHQ) between 17th and 19th February 2020. Data were compared to a sociodemographically similar sample of preschoolers (included in the 11 preschools) in 2018. Compared to the 2018 sample, the confined preschoolers demonstrated changes in sleep patterns characterized by later bedtimes and wake times, longer nocturnal and shorter nap sleep durations, comparable 24-hr sleep duration, and fewer caregiver-reported sleep disturbances. Moreover, behavioural practices (sleeping arrangement, reduced electronic device use, regular diet) and parenting practices (harmonious family atmosphere and increased parent-child communication) were associated with less sleep disturbances in the confined sample. The present study provides the first description of the impact of prolonged home confinement during the COVID-19 outbreak on sleep patterns and sleep disturbances in preschoolers, as well as highlighting the importance of the link between sleep health and family factors. Given that disrupted and insufficient sleep has been linked to immune system dysfunction, our findings also have potential implications for resilience to infection in young children during the COVID-19 pandemic. Future studies should further explore deficient sleep as a risk factor for coronavirus infection.

Desulfonylative Electrocarboxylation with Carbon Dioxide.

Electrocarboxylation of organic halides is one of the most investigated electrochemical approaches for converting thermodynamically inert carbon dioxide (CO2) into value-added carboxylic acids. By converting organic halides into their sulfone derivatives, we have developed a highly efficient electrochemical desulfonylative carboxylation protocol. Such a strategy takes advantage of CO2 as the abundant C1 building block for the facile preparation of multifunctionalized carboxylic acids, including the nonsteroidal anti-inflammatory drug ibuprofen, under mild reaction conditions.

Photothermal-Promoted Morphology Transformation in Vivo Monitored by Photoacoustic Imaging.

The in situ construction of the nanoassembly has been demonstrated to improve the performance of bioactive molecules, but the control of the morphology of nanomaterials in vivo still remains a tremendous challenge. Herein, a photothermal-promoted morphology transformation (PMT) strategy is developed to accelerate the formation of nanomaterials for improving the biological performance of drug molecules. Compared with the spontaneous process, the rate of transformation increases by ∼4 times in the PMT process. Owing to increased assembly rate, the tumor accumulation of drugs is ∼2-fold than that without photo irradiation, which inhibits tumor growth effectively. More importantly, the chemical reassembly process in vitro and in vivo is monitored by the advanced ratiometric photoacoustic image, confirming the photoinduced transformation acceleration. Through the noninvasively artificial control on assembly dynamics in vivo, the PMT strategy provides a new insight for developing the intelligent theranostics.

Subacute safety assessment of recombinant Lactococcus lactis on the gut microbiota of male Sprague-Dawley rats.

BACKGROUND: Lactococcus lactis strain pGSMT/MG1363 is a genetically modified microorganism (GMM) that constitutively expresses human metallothionein-I fusion protein to combine with intracellular lead. Unlike traditional probiotics, pGSMT/MG1363 lacks a history of safe use in food. Administration of microorganism could influence the gut microbial community and consequently confer health benefits or cause disadvantages to the host. To date, little has been done to assess the influence of recombinant strain pGSMT/MG1363 on the stability of gut microbiota. RESULTS: Liver, testis and kidney sections of male Sprague-Dawley rats orally administered pGSMT/MG1363 for 6 weeks showed normal structure and no pathological damage. There were no adverse effects on the analyzed serum biochemical parameters between the pGSMT/MG1363 group and the MG1363 group. Principal coordinate analysis showed that, compared with the MG1363 group, the 6-week-old fecal gut microbiota of rats fed with pGSMT/MG1363 was not significantly different (Adonis, P = 0.802). pGSMT/MG1363 treatment for 6 weeks did not significantly change the relative abundance of gut microbiota at the phylum and genus levels in comparison with MG1363 treatment. CONCLUSION: Compared to the non-GM strain MG1363 group, administration of the recombinant strain pGSMT/MG1363 for 6 weeks showed no adverse effects on the analyzed physiological parameters and gut microbial compositions of male Sprague-Dawley rats. The results suggested that, in terms of gut microbiota stability, pGSMT/MG1363 could be considered as safe as MG1363, at least for short-term intake. Further toxicological evaluations still need to be considered before drawing a definite conclusion concerning the safe use of pGSMT/MG1363. © 2021 Society of Chemical Industry.

Glutathione Conjugation and Protein Adduction by Environmental Pollutant 2,4-Dichlorophenol In Vitro and In Vivo.

2,4-Dichlorophenol (2,4-DCP), an environmental pollutant, was reported to cause hepatotoxicity. The biochemical mechanisms of 2,4-DCP induced liver injury remain unknown. The present study showed that 2,4-DCP is chemically reactive and spontaneously reacts with GSH and bovine serum albumin to form GSH conjugates and BSA adducts. The observed conjugation/adduction apparently involved the addition of GSH and departure of chloride via the ipso substitution pathway. Two biliary GSH conjugates and one urinary N-acetyl cysteine conjugate were observed in rats given 2,4-DCP. The N-acetyl cysteine conjugate was chemically synthesized and characterized by mass spectrometry and NMR. As expected, 2,4-DCP was found to modify hepatic protein at cysteine residues in vivo by the same chemistry. The observed protein adduction reached its peak at 15 min and revealed dose dependency. The new findings allowed us to better understand the mechanisms of the toxic action of 2,4-DCP.

Tellurium as the saturable absorber for the passively Q-switched laser at 1.34 µm.

The novel two-dimensional (2D) elementary tellurium is currently of great interest in optoelectronic and photonic applications. In this contribution, 2D tellurium nanosheets were successfully created by using the liquid-phase exfoliation method. With the as-prepared tellurium nanosheets as the saturable absorber (SA), we realized a passively $ Q $Q-switched ${\rm Nd} \text:{{\rm YVO}_4}$Nd:YVO4 laser operating at 1342 nm with a pulse width of 947 ns and single pulse energy of 2.25 µJ. Our work indicated the tellurium SA could be an efficient $ Q $Q-switcher for a near-infrared solid-state laser.

Recombinant Butelase-Mediated Cyclization of the p53-Binding Domain of the Oncoprotein MdmX-Stabilized Protein Conformation as a Promising Model for Structural Investigation.

Cyclization of the polypeptide backbone has proven to be a powerful strategy for enhancing protein stability for fundamental research and pharmaceutical application. The use of such an approach is restricted by how well a targeted polypeptide can be efficiently ligated. Recently, an Asx-specific peptide ligase identified from a tropical cyclotide-producing plant and named butelase 1 exhibited excellent cyclization kinetics that cannot be matched by other known ligases, including intein, PATG, PCY1, and sortase A. In this work, we aimed to examine whether butelase 1 facilitated protein conformational stability for structural investigation. First, we successfully expressed recombinant butelase 1 (rBTase) in the yeast Pichia pastoris. Next, rBTase was shown to be highly efficient in the cyclization of the p53-binding domain (N-terminal domain) of murine double minute X (N-MdmX), an important target for designing anticancer drugs. The cyclized N-MdmX (cMdmX) exhibited increased conformational stability and improved interaction with the ligand compared with those of noncyclized N-MdmX. Importantly, the thermal melting process was completely reversible, contrary to noncyclized N-MdmX, and the melting temperature ( Tm) of cMdmX was increased to 47 from 43 °C. This stable conformation of cMdmX was further confirmed by 15N-1H heteronuclear single-quantum coherence nuclear magnetic resonance (NMR) spectroscopy. The complex of cMdmX and the ligand was tested for protein crystallization, and several promising findings were revealed. Therefore, our work not only provides a recombinant version of butelase 1 but also suggests a conventional approach for preparing stable protein samples for both protein crystallization and NMR structural investigation.

Identification of Ketene-Reactive Intermediate of Erlotinib Possibly Responsible for Inactivation of P450 Enzymes.

Erlotinib (ELT), a tyrosine kinase inhibitor, is widely used for the treatment of nonsmall cell lung cancer in clinic. Unfortunately, severe drug-induced liver injury and other adverse effects occurred during the treatment. Meanwhile, ELT has been reported to be a mechanism-based inactivator of cytochrome P450(CYPs) 3A4 and 3A5. The objectives of this study were to identify ketene intermediate of ELT and investigate the association of the acetylenic bioactivation with the enzyme inactivation caused by ELT. A ketene intermediate was detected in human microsomal incubations of ELT, using 4-bromobenzylamine as a trapping agent. CYPs 3A4 and 3A5 mainly contributed to the bioactivation of ELT. Microsomal incubation study showed that the ketene intermediate covalently modified the enzyme protein at lysine residues and destroyed the structure of heme. The vinyl and ethyl analogs of ELT showed minor enzyme inhibitory effect (less than 20%), whereas ELT inactivated more than 60% of the enzyme. The present study provided a novel bioactivation pathway of ELT and facilitated the understanding of the mechanisms of ELT-induced mechanism-based enzyme inactivation and liver injury.

Perfluorinated substance assessment in sediments of a large-scale reservoir in Danjiangkou, China.

The occurrence of eight perfluorinated compounds (PFCs) in the surface sediments from 10 sampling sites spread across the Danjiangkou Reservoir was investigated by isotope dilution ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) after solid-phase extraction (SPE). All the sediments from the 10 sites contained detectable levels of PFCs. The total concentration of the target PFCs in each sediment sample (C∑PFCs) ranged from 0.270 to 0.395 ng g-1 of dry weight, and the mean value of C∑PFCs was 0.324 ± 0.045 ng g-1 of dry weight for the whole reservoir. For each perfluorinated compound in one sediment, perfluorooctane sulfonate (PFOS) or perfluoro-n-butanoic acid (PFBA) consistently had a higher concentration than the other six PFCs, while perfluoro-n-octanoic acid (PFOA) was always undetectable. In terms of spatial distribution, the total and individual concentrations of PFCs in sediment from downstream sites of the Danjiangkou Reservoir were higher than those from upstream sites. Factor analysis revealed that PFCs in the sediment samples originated from electroplating and anti-fog agents in industry, food/pharmaceutical packaging and the water/oil repellent paper coating, and the deposition process. The quotient method was utilized to assess the ecological risk of PFCs in the sediments of the Danjiangkou Reservoir, which showed that the concentrations of PFCs were not considered a risk. In this study, detailed information on the concentration level and distribution of PFCs in the sediments of the Danjiangkou Reservoir, which is the source of water for the Middle Route Project of the South-to-North Water Transfer Scheme in China, was reported and analyzed for the first time. These results can provide valuable information for water resource management and pollution control in the Danjiangkou Reservoir.