An Hsp70 promoter-based mouse for heat shock-induced gene modulation.

Physical therapy is extensively employed in clinical settings. Nevertheless, the absence of suitable animal models has resulted in an incomplete understanding of the in vivo mechanisms and cellular distribution that respond to physical stimuli. The objective of this research was to create a mouse model capable of indicating the cells affected by physical stimuli. In this study, we successfully established a mouse line based on the heat shock protein 70 (Hsp70) promoter, wherein the expression of CreERT2 can be induced by physical stimuli. Following stimulation of the mouse tail, ear, or cultured calvarias with heat shock (generated by heating, ultrasound, or laser), a distinct Cre-mediated excision was observed in cells stimulated by these physical factors with minimal occurrence of leaky reporter expression. The application of heat shock to Hsp70-CreERT2; FGFR2-P253R double transgenic mice or Hsp70-CreERT2 mice infected with AAV-BMP4 at calvarias induced the activation of Cre-dependent mutant FGFR2-P253R or BMP4 respectively, thereby facilitating the premature closure of cranial sutures or the repair of calvarial defects. This novel mouse line holds significant potential for investigating the underlying mechanisms of physical therapy, tissue repair and regeneration, lineage tracing, and targeted modulation of gene expression of cells in local tissue stimulated by physical factor at the interested time points. KEY MESSAGES: In the study, an Hsp70-CreERT2 transgenic mouse was generated for heat shock-induced gene modulation. Heat shock, ultrasound, and laser stimulation effectively activated Cre expression in Hsp70-CreERT2; reporter mice, which leads to deletion of floxed DNA sequence in the tail, ear, and cultured calvaria tissues of mice. Local laser stimuli on cultured calvarias effectively induce Fgfr2-P253R expression in Hsp70-mTmG-Fgfr2-P253R mice and result in accelerated premature closure of cranial suture. Heat shock activated AAV9-FLEX-BMP4 expression and subsequently promoted the repair of calvarial defect of Hsp70-CreERT2; Rosa26-mTmG mice.

How to perceive and map the synergy between CO2 and air pollutants: Observation, measurement, and validation from a case study of China.

Cities occupy a central position in addressing climate change and promoting sustainable regional development. Synergistic control of urban gas emissions at the city level is one of the main issues typically explored. The confounding effect and the interactions between the urban indicators of population and area have been ignored in previous studies. In this study, we examined the spatial distribution characteristics and synergy between greenhouse gases (CO2) and air pollutants (SO2 and NOX) using spatial population and gas emission data. By upgrading the city clustering algorithm (CCA), we established a method for defining active areas of gas emissions (spatial element-coupled clustering, SECC) and identified active areas of gas emissions in China. In this study, we created a research framework that can simultaneously consider the effects of population and area, as well as the possible interactions between these indicators in active areas. The superlinear scaling relationship between the above three gases was revealed at the active zone level, and the existence of synergy between the emission patterns of the three gases was confirmed. Via further model application, we measured the synergistic efficiency of the three gases. It was found that for every 1% increase in SO2 and NOX in an active zone, CO2 increases by 0.86%. In this study, we explored a new perspective and approach to explain the synergy between greenhouse gases and air pollutants. This is essential to promote national competition among cities to achieve synergistic control of CO2 and local air pollutants.

An Ultra-Low-Power Analog Multiplier-Divider Compatible with Digital Code for RRAM-Based Computing-in-Memory Macros.

This manuscript presents an ultra-low-power analog multiplier-divider compatible with digital code words, which is applicable to the integrated structure of resistive random-access memory (RRAM)-based computing-in-memory (CIM) macros. Current multiplication and division are accomplished by a current-mirror-based structure. Compared with digital dividers to achieve higher precision and operation speed, analog dividers present the advantages of a reduced power consumption and a simple circuit structure in lower precision operations, thus improving the energy efficiency. Designed and fabricated in a 55 nm CMOS process, the proposed work is capable of achieving 8-bit precision for analog current multiplication and division operations. Measurement results show that the signal delay is 1 µs when performing 8-bit operation, with a bandwidth of 1.4 MHz. The power consumption is less than 6.15 µW with a 1.2 V supply voltage. The proposed multiplier-divider can increase the operation capacity by dividing the input current and digital code while reducing the power consumption and complexity required by division, which can be further utilized in real-time operation of edge computing devices.

Tubular Polypyrrole with Chloride Ion Dopants as an Ultrafast Organic Anode for High-Power Lithium-Ion Batteries.

Polypyrrole (PPy), as a representative p-type conductive polymer, attracts wide attention for energy storage materials. However, the sluggish reaction kinetics and low specific capacity of PPy impede its application in high-power lithium-ion batteries (LIBs). Herein, tubular PPy with chloride and methyl orange (MO) anionic dopants is synthesized and investigated as an anode for LIBs. The Cl- and MO anionic dopants can increase the ordered aggregation and the conjugation length of pyrrolic chains, forming plentiful conductive domains and affecting the conduction channel inside the pyrrolic matrix, thereby achieving fast charge transfer and Li+ ion diffusion, low ion transfer energy barriers, and rapid reaction kinetics. On account of the above synergistic effect, PPy electrodes deliver a high specific capacity of 2067.8 mAh g-1 at 200 mA g-1 and a remarkable rate capacity of 1026 mAh g-1 at 10 A g-1 , realizing high energy density (724 Wh kg-1 ) and power density (7237 W kg-1 ) simultaneously.

Single nanowire-based fluorescence lifetime thermometer for simultaneous measurement of intra- and extra-cellular temperatures.

A silicon nanowire-based fluorescence lifetime thermometer (NWFLT) was fabricated for the simultaneous measurement of intra- and extra-cellular temperatures. Using the NWFLT, an obvious heterogeneity of the temperature was found along the longitude direction of the NWFLT, especially between the inside and outside of the cell.

Psychological Resilience and Coping Strategies with Anxiety among Malaysian Medical Students during the COVID-19 Pandemic.

Coronavirus Disease 2019 (COVID-19) swept the world by storm and caused a myriad of devastating consequences, particularly disruptions in medical education. This study aims to examine the association between sociodemographic factors, psychological factors, coping strategies and anxiety among medical students, as well as to identify the predictors of anxiety among them. A cross-sectional study design was used. Self-rated Rosenberg Self-Esteem Scale (RSES), General Self-Efficacy Scale (GSES), Brief Coping Orientation to Problems Experienced Scale (Brief COPE), and General Anxiety Disorder-7 Scale (GAD-7) were used. A total of 371 respondents from a tertiary education center were recruited. The prevalence of anxiety was 37% which corresponded to 21.6% and 15.4% for moderate and severe anxiety, respectively. Sociodemographic factors such as age group and academic year were significantly associated with anxiety, while those with higher self-esteem (rs = -0.487), self-competence (rs = -0.407), self-liking (rs = -0.499), and self-efficacy (rs = -0.245) had lower anxiety. Inversely, those who adopted emotion-focused (rs = 0.130) and dysfunctional coping styles (rs = 0.559) showed higher anxiety. The main predictors of anxiety were self-liking as a protective factor (aOR = 0.81) and dysfunctional coping as a risk factor (aOR = 1.16). Therefore, resilience building and inculcating positive coping strategies are imperative in equipping our budding healthcare providers to weather through future unforeseeable disasters.

The spatial configuration of buildings: A vital consideration impossible to ignore in regulating urban land surface temperature? Evidence from 35 Chinese cities.

Land urbanization not only efficiently met the requirements of social development but also brought severe heating effects, especially the changes in Land Surface Temperature (LST). The effects of building density on LST and driving relation of the configuration of buildings remain poorly understood over large areas. Using Landsat 8 satellite imagery acquired from the summer of 2019, this study quantified the heating effects (k) of building density on LST across 35 cities in China, and further analyzed the driving relation of the configuration of buildings such as the size, shape, and spatial distribution on k. Here the regression analysis results showed that the building density had a significant relationship with LST, and the k varied from 1.10 to 7.27 amount of the different cities. The size and aggregation distribution of buildings were the main positive drivers for the effects of building density on LST, and the shape of buildings was not obviously related to the k-value. The results of thermal environment simulation showed that the major reason might be that the close spatial relationship reduced the heat exchange between buildings and the atmosphere, resulting in higher LST. These conclusions will provide an important reference for urban planning and design.

A new method of hotspot analysis on the management of CO2 and air pollutants, a case study in Guangzhou city, China.

Emission inventory plays an important role in designing effective emission control strategies. Currently, there is unbalanced development of CO2 and air pollutant emission inventories in China and the spatial information of both cannot be obtained simultaneously, which prevents a collaborative control strategy. In this study, we developed a unified emission inventory including both CO2 and air pollutants, then utilized spatial mapping methods to identify the co-hotspots of both CO2 and air pollutants at a high spatial resolution (1 × 1 km2). We applied Guangzhou city as a case study to illustrate the method. The results showed that CO2 and air pollutants were mainly emitted from the stationary combustion sector and the transportation sector. These two sectors contributed 95 %, 67 %, and 93 % to total CO2, SO2, and NOx emissions, respectively. Up to 86 %, 86 %, 66 %, and 72 % of total CO2, SO2, NOx, and PM2.5 emissions were attributed to the top 10 % emission grids with 1 × 1 km2 resolution. However, our results showed high emission grids were not surrounded by other high emissions grids for all types of emissions analyzed in this study. The co-hotspot analysis enables accurate identification of high-emission grids, which helps environment managers to prioritize resource allocation when designing control strategies. Our study underscores the importance of managing CO2 and air pollutants simultaneously at the city level.

Tunable Berreman mode in highly conductive organic thin films.

The unique performances of Epsilon-near-zero (ENZ) materials allow them to play a crucial role in many optoelectronic devices and have spawned a wide range of inventive uses. In this paper, we found that the modified PEDOT:PSS film formed with a kind of so-called "Metastable liquid-liquid Contact (MLLC)" solution treatment method can achieve a wide tuning of ENZ wavelength from 1270 nm to 1550 nm in the near-infrared region. We further analyzed the variation trend of imaginary permittivity for these samples with different ENZ wavelengths. The Berreman mode was successfully excited by a simple structural design to realize a tunable polarization absorber.

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH4I.

The electrochemical preparation of 2-aminothiazoles has been achieved by the reaction of active methylene ketones with thioureas assisted by ᴅʟ-alanine using NH4I as a redox mediator. The electrochemical protocol proceeds in an undivided cell equipped with graphite plate electrodes under constant current conditions. Various active methylene ketones, including ß-keto ester, ß-keto amide, ß-keto nitrile, ß-keto sulfone and 1,3-diketones, can be converted to the corresponding 2-aminothiazoles. Mechanistically, the in situ generated α-iodoketone was proposed to be the key active species.

Simultaneous Monitoring of the Adenosine Triphosphate Levels in the Cytoplasm and Nucleus of a Single Cell with a Single Nanowire-Based Fluorescent Biosensor.

Simultaneous monitoring of the ATP levels at various sites of a single cell is crucial for revealing the ATP-related processes and diseases. In this work, we rationally fabricated single nanowire-based fluorescence biosensors, by which the ATP levels of the cytoplasm and nucleus in a single cell can be simultaneously monitored with a high spatial resolution. Utilizing the as-fabricated single nanowire biosensor, we demonstrated that the ATP levels of the cytoplasm were around 20-30% lower than that of the nucleus in both L929 and HeLa cells. Observing the ATP fluctuation of the cytoplasm and nucleus of the L929 and HeLa cells stimulated by Ca2+, oligomycin, or under cisplatin-induced apoptosis, we found that the ATP levels at two cellular sites exhibited discriminative changes, revealing the different mechanisms of the ATP at these two cellular sites in response to the stimulations.

A perception of the nexus "resistance, recovery, resilience" of vegetations responded to extreme precipitation pulses in arid and semi-arid regions: A case study of the Qilian Mountains Nature Reserve, China.

Unprecedented pulses of extreme precipitation due to climate change are causing significant stresses and impacts on regional and even global ecosystems. However, the relationship of vegetation response to this disturbance is unclear, such as phase characteristics, extent, timing, and degree. We summarize the nexus between vegetation resistance, recovery, and resilience under three stages of extreme precipitation pulses: duration, lagging, and post-disturbance, and then construct a pragmatic scheme to quantify and validate this complex relationship based on precipitation and Normalized Difference Vegetation Index (NDVI) data for the Qilian Mountains Nature Reserve (QMNR) from 2000 to 2020. The results show that the four extreme precipitation pulses were spring 2010 (118.98 mm), summer 2007 (312.25 mm), autumn 2010 (109.74 mm), and winter 2018 (6.84 mm). Extreme precipitations had a significant effect on vegetation in at least 98.5 % of the area, and there was also a two-month time lag effect. Specifically, the percentage of negative vegetation resistance in the face of four seasons of extreme precipitation pulses was 18.3 %, 2.0 %, 15.4 %, and 21.7 %, respectively, compared to negative recovery rates of 4.8 %, 11.9 %, 17.8 % and 10.2 % respectively, resilience was even more severe, with 20.1 %, 10.9 %, 16.1 % and 16.3 % of vegetation failing to rebound to normal levels within two months. The negative resistance, negative recovery, and weak resilience of vegetation under short-term extreme precipitation pulses are approximately 4.8, 3.7, and 5.3 times more fierce than long-term vegetation degradation. A total of 62 % of the four seasonal areas of severe negative resistance, severe negative recovery, and weak resilience were located in areas of moderate and significant steepness, which confirms that extreme precipitation pulses cause serious degradation of vegetation. Response of vegetation under extreme precipitation pulses is perceived, quantified, and validated in this study, which is essential for addressing climate change.

Expansion of FGFR3-positive nucleus pulposus cells plays important roles in postnatal nucleus pulposus growth and regeneration.

BACKGROUND: Intervertebral disc degeneration (IVDD) can cause low back pain, a major public health concern. IVDD is characterized with loss of cells especially those in nucleus pulposus (NP), due to the limited proliferative potential and regenerative ability. Few studies, however, have been carried out to investigate the in vivo proliferation events of NP cells and the cellular contribution of a specific subpopulation of NP during postnatal growth or regeneration. METHODS: We generated FGFR3-3*Flag-IRES-GFP mice and crossed FGFR3-CreERT2 mice with Rosa26-mTmG, Rosa26-DTA and Rosa26-Confetti mice, respectively, to perform inducible genetic tracing studies. RESULTS: Expression of FGFR3 was found in the outer region of NP with co-localized expressions of proliferating markers. By fate mapping studies, FGFR3-positive (FGFR3+) NP cells were found proliferate from outer region to inner region of NP during postnatal growth. Clonal lineage tracing by Confetti mice and ablation of FGFR3·+ NP cells by DTA mice further revealed that the expansion of the FGFR3+ cells was required for the morphogenesis and homeostasis of postnatal NP. Moreover, in degeneration and regeneration model of mouse intervertebral disc, FGFR3+ NP cells underwent extensive expansion during the recovery stage. CONCLUSION: Our present work demonstrates that FGFR3+ NP cells are novel subpopulation of postnatal NP with long-existing proliferative capacity shaping the adult NP structure and participating in the homeostasis maintenance and intrinsic repair of NP. These findings may facilitate the development of new therapeutic approaches for IVD regeneration.

The antibacterial activity of a novel NK-lysin homolog and its molecular characterization and expression in the striped catfish, Pangasianodon hypophthalmus.

Aeromonas hydrophila was a common bacterial pathogen in aquaculture resulting in considerable losses to the striped catfish aquaculture industry. As an emergent antimicrobial peptide (AMP), NK-lysin (NKL) had activity against various microorganisms. However, the antibacterial activity of NKL from striped catfish (Pangasianodon hypophthalmus) both in vitro and vivo remains unclear. In this study, the cDNA sequence of P. hypophthalmus NK-lysin gene (PhNK-lysin) was cloned and characterized. The amino acid sequence of PhNK-lysin contains a signal peptide sequence of 17 amino acid (aa) residues and a mature peptide composed of 130 aa. The saposin B domain of mature peptide comprised six conserved cysteines forming three putative disulfide bonds. Phylogenetic analysis revealed that the PhNK-lysin was most closely related to that of the channel catfish (Ictalurus punctatus) NK-lysin. The transcriptional levels of the PhNK-lysin were significantly upregulated in response to A. hydrophila infection in various tissues including heart, liver, spleen, head kidney, trunk kidney and gill. The synthetic PhNK-lysin-derived peptide consisting of 38aa showed antibacterial activity against Vibrio harveii, Aeromonas hydrophila and Escherichia coli. The MIC for V. harveii, A. hydrophila and E. coli were 15.625 µM, 250 µM and 31.25 µM respectively. Besides, the synthetic PhNK-lysin decreased the bacterial load of liver and trunk kidney in vivo as well as increased the survival rate of A. hydrophila infected striped catfish. Hence, these data suggest that PhNK-lysin had antimicrobial effect and protects the host from pathogenic infection.

A Facile Preparation of Multicolor Carbon Dots.

Carbon dots (CDs) have raised broad interest because of their great potential in the fluorescence related fields, such as photocatalysis and bioimaging. CDs exhibit different optical properties when dissolved in various solvents. However, the effects of solvents during the process of preparation on the fluorescence emission of CDs are still unclear. In this work, CDs were prepared by a simple one-pot solvothermal route. Typical critic acid and thiourea were used as precursors. Through changing the volume ratio of water to N,N-dimethylformamide (DMF), we have obtained color tunable CDs, with the emission wavelength from 450 to 640 nm. TEM images, Raman and XPS spectra indicate that the particle size of CDs and the content of surface functional groups (C-N/C-S and C≡N bonds) increase with the increasing ratio of DMF to water, which results in the optimal emission wavelength red-shifted. The prepared multicolor CDs may have prospects in the lighting applications.

Sensitive and Stable Thermometer Based on the Long Fluorescence Lifetime of Au Nanoclusters for Mitochondria.

Detecting the temperature of intracellular mitochondria with high sensitivity and stability is crucial to understanding the cellular metabolism and revealing the processes of mitochondria-related physiology. In this paper, employing the long fluorescence lifetime of modified Au nanoclusters (mAuNCs) by 4-(carboxybutyl) triphenylphosphonium bromide, we developed a fluorescence lifetime thermometer with high sensitivity and stability for the temperature of the intracellular mitochondria. A high relative temperature sensitivity of 2.8% and excellent photostability were achieved from the present thermometer. After incubation with L929 cells, the mAuNCs could be endocytosed into the cells and targeted the mitochondria, and the temperature changes at the L929 cells' mitochondria, which were stimulated by carbonyl cyanide 3-chlorophenylhydrazone and Ca2+, were successfully detected via the fluorescence lifetime images of the mAuNCs. Furthermore, utilizing the mAuNCs, we clarified the effect of Mg2+ on the temperature of the intracellular mitochondria. The strategy of employing a material with a long fluorescence lifetime and remarkable stability to fabricate the fluorescence lifetime thermometer for mitochondria can be used to design various thermometers for other organelles.

Electrochemical Oxidative C3 Acyloxylation of Imidazo[1,2-a]pyridines with Hydrogen Evolution.

The C3-functionalized imidazo[1,2-a]pyridines are versatile nitrogen-fused heterocycles; however, the methods for the C3 acyloxylation of imidazo[1,2-a]pyridines have never been reported. Herein we demonstrate the electrochemical oxidative C3 acyloxylation of imidazo[1,2-a]pyridines for the first time. Notably, by using electricity, the electrochemical oxidative C3 acyloxylation of imidazo[1,2-a]pyridines was carried out under mild conditions. Moreover, in addition to aromatic carboxylic acids, alkyl carboxylic acids were also competent substrates.

Effect of 405-nm light-emitting diode on environmental tolerance of Cronobacter sakazakii in powdered infant formula.

Cronobacter sakazakii is an opportunistic pathogen that can survive extreme desiccation, heat, acid, and osmotic stress. This can increase the risk of infection, resulting in severe diseases, mainly in neonates. The inactivation effect of 405 ± 5-nm light-emitting diode (LED) illumination on C. sakazakii with different initial concentrations and C. sakazakii strains isolated from powdered infant formula (PIF) and baby rice cereal (BRC) were firstly evaluated. Then, the effect of 405 ± 5-nm LED on the tolerance of diverse environmental conditions of C. sakazakii in PIF was investigated. Conditions involving desiccation [PIF, Water activity (aw): 0.2-0.5], heat (45, 50, and 55 °C), acid (simulated gastric fluid: SGF, pH 4.75 ± 0.25), and bile salt (0.2%, bile salt solution) were used to study the effects of 405-nm LED on C. sakazakii resistance. The transcription levels of ten tolerance-associated genes and changes in bacterial cell membrane were examined to understand the response of C. sakazakii to LED illumination. The results showed that 405-nm LED effectively inactivated C. sakazakii ATCC 29544 with initial concentration from 8 to 1 log CFU/g in PIF and strains isolated from PIF and BRC. Moreover, 405-nm LED could decrease the tolerance of C. sakazakii in PIF to desiccation, heat treatment at 50 and 55 °C, SGF, and bile salt to different degrees, but the resistance to the heat treatment at 45 °C was not influenced by LED illumination. In addition, the transcription levels of the ten tolerance-associated genes measured in the LED-illuminated C. sakazakii cells were significantly downregulated compared with those in unilluminated controls. The damage on cell membrane was confirmed for LED-treated cells by LIVE/DEAD® assay. These results indicate that 405-nm LED illumination may be effective at reducing the environmental resistance of C. sakazakii in PIF. Furthermore, this study suggests the potential for applying 405-nm LED technology in the prevention and control of pathogens in food processing, production, and storage environments.

Convenient Preparation of N-Acylbenzoxazines from Phenols, Nitriles, and DMSO Initiated by a Catalytic Amount of (COCl)2.

A convenient preparation method of N-acylbenzoxazines has been developed, in which phenols react with nitriles and dimethyl sulfoxide (DMSO) in the presence of a catalytic amount of (COCl)2 in CH3CN or chloroform to afford the corresponding N-acylbenzoxazines in moderate-to-good yields. DMSO acts as a source of HCHO, which is generated in situ from the decomposition of a methoxydimethylsulfonium salt. A regeneration cycle of the methoxydimethylsulfonium salt is proposed, which is initiated by a catalytic amount of (COCl)2.

Electrochemical synthesis of versatile ammonium oxides under metal catalyst-, exogenous-oxidant-, and exogenous-electrolyte-free conditions.

An electrochemical oxidative cross-coupling reaction between 2.5-substituted-pyrazolin-5-ones and ammonium thiocyanate has been developed, which resulted in a series of unprecedented cross-coupling products under metal catalyst-, exogenous-oxidant-, and exogenous-electrolyte-free conditions. It is worth noting that since the resulting cross-coupling products are nearly insoluble in MeCN, the pure product could be afforded without silica gel column purification. In addition, the prepared ammonium oxides are versatile building blocks for synthesizing functionalized pyrazole derivatives.