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Objectives: To investigate the clinical and molecular epidemiological characteristics of blaIMP-4-carrying Klebsiella pneumoniae in a tertiary hospital in China. Methods: Ten carbapenem-resistant K. pneumoniae (CRKP) isolates carrying the blaIMP-4 gene were collected. Molecular characteristics were analysed using whole-genome sequencing. Plasmid conjugation experiments were used to analyse conjugation of the plasmids. We compared and analysed K. pneumoniae-carrying blaIMP-4 genomic datasets obtained from the National Center for Biotechnology Information (NCBI) with the strains in this study. Results: All 10 CRKP isolates carrying blaIMP-4 were collected from 10 adult patients in the respiratory intensive care unit. These strains were only sensitive to polymyxins and tigecycline due to them simultaneously carrying multiple resistance genes, namely blaOKP-A-5, fosA, oqxA, and oqxB. Notably, R29 harboured two carbapenemase genes (blaNDM-1 and blaIMP-4). These strains had similar drug-resistant phenotypes and genes, all belonging to sequence type (ST)196. Additionally, the patients had experienced spatiotemporal intersection during hospitalization, suggesting that these strains underwent clonal transmission, but they belonged to different clonal clusters from the blaIMP-4-positive K. pneumoniae currently published in the NCBI. Among the 10 strains, blaIMP-4 was located on the IncN plasmid, and six strains had successfully transferred the plasmid to the recipient strain EC600 through plasmid conjugation. Conclusions: The blaIMP-4-positive ST196 CRKP isolate showed clonal distribution in the respiratory intensive care unit, which was mediated by the IncN plasmid. Consequently, there should be increased monitoring of carbapenem-resistant strains in clinical settings to prevent and control its transmission.

Abstract The issue of brightness in strong ambient light conditions is one of the critical obstacles restricting the application of augmented reality (AR) and mixed reality (MR). Gallium nitride (GaN)-based micro-LEDs, renowned for their exceptional brightness and stability, are considered the foremost contenders for AR applications. Nevertheless, conventional heteroepitaxial growth micro-LED devices confront formidable challenges, including substantial wavelength shifts and efficiency droop. In this paper, we firstly demonstrated the high-quality homoepitaxial GaN-on-GaN micro-LEDs micro-display, and thoroughly analyzed the possible benefits for free-standing GaN substrate from the material-level characterization to device optoelectronic properties and micro-display application compared with sapphire substrate. The GaN-on-GaN structure exhibits a superior crystal quality with ultra-low threading dislocation densities (TDDs) of ~ 105 cm−2, which is three orders of magnitude lower than that of GaN-on-Sapphire. Through an in-depth size-dependent optoelectronic analysis of blue/green emission GaN-on-GaN/ Sapphire micro-LEDs from 100 × 100 shrink to 3 × 3 μm2, real that a lower forward voltage and series resistance, a consistent emission wavelength (1.21 nm for blue and 4.79 nm for green @ 500 A/cm2), coupled with a notable reduction in efficiency droop ratios (15.6% for blue and 28.5% for green @ 500 A/cm2) and expanded color gamut (103.57% over Rec. 2020) within GaN-on-GaN 10 μm micro-LEDs. Last but not least, the GaN-on-GaN micro-display with 3000 pixels per inch (PPI) showcased enhanced display uniformity and higher luminance in comparison to its GaN-on-Sapphire counterpart, demonstrating significant potentials for high-brightness AR/MR applications under strong ambient light.

The lithology distribution of fine-grained sedimentary rocks in regional space plays a crucial role in guiding the exploration of oil shale layers. Identifying lithology by conventional logging information is efficient and cost-effective. However, the strong inhomogeneity of fine-grained sedimentary rocks leads to a complex nonlinear relationship between lithology and logging data, making conventional linear methods no longer applicable. This study proposes a hybrid model for logging lithology identification of fine-grained sedimentary rocks from the first member of Qingshankou Formation in the Songliao Basin, NE China. This model is based on the hybrid kernel extreme learning machine (HKELM), and the firefly perturbation strategy is introduced into the sparrow search algorithm (FSSA) for optimization. The lithologic distribution is determined using cores, thin sections, and total organic carbon (TOC), while a total of four logging curves, the acoustic (AC), density (DEN), resistivity (RT), and natural gamma (GR) curves, were collected. FSSA-HKELM was compared with five algorithms, ELM, KELM, HKELM, PSO-HKELM, and SSA-HKELM, for lithology prediction effectiveness. The proposed hybrid method outperformed the other algorithms, achieving an accuracy of 81.78%, precision of 81.65%, recall of 87.78%, and a weighted F1 score of 82.16%. FSSA-HKELM is a very effective lithological identification method, which provides a basis for the lithological prediction of oil shale-bearing formations.

Abstract Sensors with a small footprint and real-time detection capabilities are crucial in robotic surgery and smart wearable equipment. Reducing device footprint while maintaining its high performance is a major challenge and a significant limitation to their development. Here, we proposed a monolithic integrated micro-scale sensor, which can be used for vector force detection. This sensor combines an optical source, four photodetectors, and a hemispherical silicone elastomer component on the same sapphire-based AlGaInP wafer. The chip-scale optical coupling is achieved by employing the laser lift-off techniques and the flip-chip bonding to a processed sapphire substrate. This hemispherical structure device can detect normal and shear forces as low as 1 mN within a measurement range of 0–220 mN for normal force and 0–15 mN for shear force. After packaging, the sensor is capable of detecting forces over a broader range, with measurement capabilities extending up to 10 N for normal forces and 0.2 N for shear forces. It has an accuracy of detecting a minimum normal force of 25 mN and a minimum shear force of 20 mN. Furthermore, this sensor has been validated to have a compact footprint of approximately 1.5 mm2, while maintaining high real-time response. We also demonstrate its promising potential by combining this sensor with fine surface texture perception in the fields of compact medical robot interaction and wearable devices.

Tensegrity robots contain compression struts and tension tendons, allowing them to change their shape by controlling the lengths of members. Due to their excellent locomotion ability, they can play well when exploring complex environments. To protect the internal devices and meanwhile provide a base layer for thin film solar cells, membranes are proposed to cover the outer surface of the locomotive tensegrity in this study. A mathematical model for locomotive tensegrity with membranes is developed. A genetic algorithm incorporated with an incremental dynamic relaxation method is used to generate rolling gaits for the locomotive tensegrity with membranes. A classical strut-actuated 6-strut tensegrity system is taken as the basic model, and eight triangular membranes are covered on its outer surface to build a typical locomotive tensegrity with membranes. The influence of the membranes on the original rolling gaits generated by a numerical model of the 6-strut locomotive tensegrity without membranes is investigated. It is found that the effect of membranes becomes negligible when the relative stiffness between membranes and tendons is equal to or less than 1.2. When the effect of membranes is not negligible, the rolling gaits of the 6-strut locomotive tensegrity with membranes should be redesigned by using a numerical model taking the membranes into account. A physical prototype for the strut-actuated 6-strut locomotive tensegrity with membranes is fabricated, and tested to verify the feasibility of the redesigned rolling gaits.

Cognitive behavioral stress management (CBSM) relieves physical and psychological burdens in patients with some central nervous system diseases, while its utility in acute ischemic stroke (AIS) patients is unclear. This study aimed to explore the effect of CBSM on neurologic recovery and psychosomatic health in AIS patients. Totally, 176 naive AIS patients were randomized into routine care (RC) group (n=88) and CBSM group (n=88) to receive a 3-month corresponding intervention. Modified Rankin scale (mRS) scores at the first month after discharge (M1) (P=0.008) and the third month after discharge (M3) (P=0.016) were lower in the CBSM group than in the RC group. The proportion of AIS patients with mRS score >2 at M3 was reduced in CBSM group vs RC group (P=0.045). Hospital anxiety depression scale (HADS)-anxiety score at M3 (P=0.016), HADS-depression score at M3 (P=0.005), and depression rate at M3 (P=0.021) were decreased in the CBSM group vs the RC group. EuroQol-5 dimension scores at M1 (P=0.024) and M3 (P=0.012) were decreased, while EuroQol-visual analogue scale score at M3 (P=0.026) was increased in the CBSM group vs the RC group. By subgroup analyses, CBSM had favorable outcomes in AIS patients with age ≤65 years. CBSM was beneficial to neurologic recovery and distress relief in AIS patients with an education level of middle school or above, and to health status in those with an education level of primary school or uneducated. In conclusion, CBSM benefitted neurologic recovery and psychosomatic health in AIS patients with minor neurological deficits, however, further studies should verify these results with a larger sample size and longer follow-up.

Abstract Background The role of α-synuclein in dementia has been recognized, yet its exact influence on cognitive decline in non-demented older adults is still not fully understood. Methods A total of 331 non-demented individuals were included in the study from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Participants were divided into two distinct groups based on their α-synuclein levels: one with lower levels (α-synuclein-L) and another with higher levels (α-synuclein-H). Measurements included neuropsychiatric scales, cerebrospinal fluid (CSF) biomarkers, and blood transcriptomics. The linear mixed-effects model investigated the longitudinal changes in cognition. Kaplan-Meier survival analysis and the Cox proportional hazards model were utilized to evaluate the effects of different levels of α-synuclein on dementia. Gene set enrichment analysis (GSEA) was utilized to investigate the biological pathways related to cognitive impairment. Pearson correlation, multiple linear regression models, and mediation analysis were employed to investigate the relationship between α-synuclein and neurodegenerative biomarkers, and their potential mechanisms affecting cognition. Results Higher CSF α-synuclein levels were associated with increased risk of cognitive decline and progression to dementia. Enrichment analysis highlighted the activation of tau-associated and immune response pathways in the α-synuclein-H group. Further correlation and regression analysis indicated that the CSF α-synuclein levels were positively correlated with CSF total tau (t-tau), phosphorylated tau (p-tau) 181, tumor necrosis factor receptor 1 (TNFR1) and intercellular cell adhesion molecule-1 (ICAM-1). Mediation analysis further elucidated that the detrimental effects of CSF α-synuclein on cognition were primarily mediated through CSF t-tau and p-tau. Additionally, it was observed that CSF α-synuclein influenced CSF t-tau and p-tau181 levels via inflammatory pathways involving CSF TNFR1 and ICAM-1. Conclusions These findings elucidate a significant connection between elevated levels of CSF α-synuclein and the progression of cognitive decline, highlighting the critical roles of activated inflammatory pathways and tau pathology in this association. They underscore the importance of monitoring CSF α-synuclein levels as a promising biomarker for identifying individuals at increased risk of cognitive deterioration and developing dementia.

Abstract. Background:. Somatic copy number variations (SCNVs) in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell carcinoma. However, whether CDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia (ESCdys) is unknown. This study aimed to investigate the characteristics and prognostic value of CDKN2A SCNVs in patients with mild or moderate (m/M) ESCdys. Methods:. This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China (Ci County, Hebei Province; Yanting, Sichuan Province; Linzhou, Henan Province; Yangzhong, Jiangsu Province; and Feicheng, Shandong Province) from 2005 to 2019. Genomic DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients, and a quantitative polymerase chain reaction assay, P16-Light, was used to detect CDKN2A copy number. The cumulative regression and progression rates of ESCdys were evaluated using competing risk models. Results:. A total of 205 patients with baseline m/M ESCdys were enrolled. The proportion of ESCdys regression was significantly lower in the CDKN2A deletion cohort than in the diploid and amplification cohorts (18.8% [13/69] vs. 35.0% [28/80] vs. 51.8% [29/56], P

Background and purpose: GLP-1 receptor agonists are clinically utilized for type 2 diabetes and obesity. In vitro and in vivo preclinical studies were performed to assess the druggability of a novel small molecule GLP-1 receptor biased agonist SAL0112. Experimental approach: The HTRF assay, FLIPR assay, TR-FRET assay, and PathHunter assay were utilized for in vitro studies. Liver transporter tests were conducted using the HEK293-OATP1B1 and HEK293-OATP1B3 cell lines. In vitro stability assessments of various species and in vivo PK studies in rodents were performed. A model of type 2 diabetes and obesity induced by a high-energy diet in transgenic C57BL/6 mice expressing the human GLP-1 receptor gene was conducted. Principal results: SAL0112 demonstrated high potency and selectivity in activating the Gαs pathway of the GLP-1 receptor, with no observed desensitization. SAL0112 demonstrated greater stability in human and rat liver microsomes compared to Danuglipron. In vivo PK studies revealed higher absorption of SAL0112 in rats. SAL0112 displayed a significantly lower potential for DDI on liver transporters compared to Danuglipron. SAL0112 led to significant reductions in body weight (P

Abstract Background Pichia pastoris is a widely utilized host for heterologous protein expression and biotransformation. Despite the numerous strategies developed to optimize the chassis host GS115, the potential impact of changes in cell wall polysaccharides on the fitness and performance of P. pastoris remains largely unexplored. This study aims to investigate how alterations in cell wall polysaccharides affect the fitness and function of P. pastoris, contributing to a better understanding of its overall capabilities. Results Two novel mutants of GS115 chassis, H001 and H002, were established by inactivating the PAS_chr1-3_0225 and PAS_chr1-3_0661 genes involved in β-glucan biosynthesis. In comparison to GS115, both modified hosts exhibited a looser cell surface and larger cell size, accompanied by faster growth rates and higher carbon-to-biomass conversion ratios. When utilizing glucose, glycerol, and methanol as exclusive carbon sources, the carbon-to-biomass conversion rates of H001 surpassed GS115 by 10.00%, 9.23%, and 33.33%, respectively. Similarly, H002 exhibited even higher increases of 32.50%, 12.31%, and 53.33% in carbon-to-biomass conversion compared to GS115 under the same carbon sources. Both chassis displayed elevated expression levels of green fluorescent protein (GFP) and human epidermal growth factor (hegf). Compared to GS115/pGAPZ A-gfp, H002/pGAPZ A-gfp showed a 57.64% higher GFP expression, while H002/pPICZα A-hegf produced 66.76% more hegf. Additionally, both mutant hosts exhibited enhanced biosynthesis efficiencies of S-adenosyl-L-methionine and ergothioneine. H001/pGAPZ A-sam2 synthesized 21.28% more SAM at 1.14 g/L compared to GS115/pGAPZ A-sam2, and H001/pGAPZ A-egt1E obtained 45.41% more ERG at 75.85 mg/L. The improved performance of H001 and H002 was likely attributed to increased supplies of NADPH and ATP. Specifically, H001 and H002 exhibited 5.00-fold and 1.55-fold higher ATP levels under glycerol, and 6.64- and 1.47-times higher ATP levels under methanol, respectively, compared to GS115. Comparative lipidomic analysis also indicated that the mutations generated richer unsaturated lipids on cell wall, leading to resilience to oxidative damage. Conclusions Two novel P. pastoris chassis hosts with impaired β-1,3-D-glucan biosynthesis were developed, showcasing enhanced performances in terms of growth rate, protein expression, and catalytic capabilities. These hosts exhibit the potential to serve as attractive alternatives to P. pastoris GS115 for various bioproduction applications.

Abstract Background Recently, extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) isolates have been increasingly detected and posed great challenges to clinical anti-infection treatments. However, little is known about extensively resistant hypervirulent P. aeruginosa (XDR-hvPA). In this study, we investigate its epidemiological characteristics and provide important basis for preventing its dissemination. Methods Clinical XDR-PA isolates were collected from January 2018 to January 2023 and identified using matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry; antibiotic susceptibility testing was performed by broth microdilution method, and minimum inhibitory concentrations (MICs) were evaluated. Virulence was evaluated using the Galleria mellonella infection model; molecular characteristics, including resistance genes, virulence genes, and homology, were determined using whole-genome sequencing. Results A total of 77 XDR-PA strains were collected; 47/77 strains were XDR-hvPA. Patients aged > 60 years showed a significantly higher detection rate of XDR-hvPA than of XDR-non-hvPA. Among the 47 XDR-hvPA strains, 24 strains carried a carbapenemase gene, including bla GES−1 (10/47), bla VIM−2 (6/47), bla GES−14 (4/47), bla IMP−45 (2/47), bla KPC−2 (1/47), and bla NDM−14 (1/47). ExoU, exoT, exoY, and exoS, important virulence factors of PA, were found in 31/47, 47/47, 46/47, and 29/47 strains, respectively. Notably, two XDR-hvPA simultaneously co-carried exoU and exoS. Six serotypes (O1, O4–O7, and O11) were detected; O11 (19/47), O7 (13/47), and O4 (9/47) were the most prevalent. In 2018–2020, O4 and O7 were the most prevalent serotypes; 2021 onward, O11 (16/26) was the most prevalent serotype. Fourteen types of ST were detected, mainly ST235 (14/47), ST1158 (13/47), and ST1800 (7/47). Five global epidemic ST235 XDR-hvPA carried bla GES and showed the MIC value of ceftazidime/avibactam reached the susceptibility breakpoint (8/4 mg/L). Conclusions The clinical detection rate of XDR-hvPA is unexpectedly high, particularly in patients aged > 60 years, who are seemingly more susceptible to contracting this infection. Clonal transmission of XDR-hvPA carrying bla GES, which belongs to the global epidemic ST235, was noted. Therefore, the monitoring of XDR-hvPA should be strengthened, particularly for elderly hospitalized patients, to prevent its spread.

Abstract Sequence stratigraphy study in mudstone and oil shale strata is difficulty but critical for the analysis of the quality unconventional oil and gas reservoirs. This contribution investigates the sequence stratigraphy of the Eocene thick organic-rich fine-grained sediments in the Fushun basin, according to the organic geochemical data measured in laboratory and predicted by the amplitude difference the resistivity and the density curve when they are overlapping (which was called ΔlogR). The sampling interval of ΔlogR was 0.125 m. The results show that the total organic carbon, the oil yield, and the petroleum potential of the Eocene mudstones prove a good linear correlation between values measured in lab and values predicted by the ΔlogR model. A total of 21 parasequences are identified in mudstones and can be divided into two cycles, a fully developed lower cycle and an underdeveloped upper cycle. There are four organic matter accumulation stages in a fully developed cycle, including two stages in the uprising half-cycle characterized by low values and rising values of the predicted geochemical data, respectively, followed by two stages in the declining half cycle characterized by high values and decreasing values of the predicted geochemical data, respectively. This contribution provides a basis for a further analysis of the characteristics of organic matter cycles in the oil shale strata of the Fushun Basin and areas with similar situation.

A compact high-power 2.8-µm laser with a 2 at.%-doped Er3+:CaF2 crystal was demonstrated, which delivered a maximum output power of 2.848 W with a slope efficiency of 26.3 %. To the best of our knowledge, this is the highest output power among all the reported LD end-pumped Er3+-doped fluoride crystal lasers. Experimentally, the negative thermal lens effect was characterized and the thermal lens optical diopters for two axes were obtained as Mx = -0.21 m−1/W and My = -0.33 m−1/W. In addition, the visible fluorescence spectra of Er3+:CaF2 crystal with and without laser operation were measured and analyzed. With Fe2+:ZnSe as saturable absorber, a passively Q-switched 2.759-µm Er3+:CaF2 laser with an average output power of 75 mW, a peak power of 2.39 W, a single pulse energy of 1.81 µJ, and a pulse width of 755.3 ns was obtained at a repetition rate of 41.55 kHz.

The selection of targets with specific masses, including molecules, atoms, and clusters, has broad applications in spectrometry. As an ion mass-gate with a very high resolution, Bradbury–Nielsen Gates (BNGs) are widely used in the study of size-dependent effects of clusters. Here, wepresent a simple and low-cost method for fabricating high resolution BNGs using a printed circuit board and a 3D printed wire winding and transfer tool. It can produce a pitch of 400 µm with 25 µm diameter tungsten wires. The test results indicate that its resolution reaches more than 1500 when it couples with a homemade ultrafast voltage switch.

Abstract With the growing demand for thermal management of electronic devices, cooling of high-precision instruments, and biological cryopreservation, heat flux measurement of complex surfaces and at ultralow temperatures has become highly imperative. However, current heat flux sensors (HFSs) are commonly used in high-temperature scenarios and have problems when applied in low-temperature conditions, such as low sensitivity and embrittlement. In this study, we developed a flexible and highly sensitive HFS that can operate at ultralow to high temperatures, ranging from −196 °C to 273 °C. The sensitivities of HFSs with thicknesses of 0.2 mm and 0.3 mm, which are efficiently manufactured by the screen-printing method, reach 11.21 μV/(W/m2) and 13.43 μV/(W/m2), respectively. The experimental results show that there is a less than 3% resistance change from bending to stretching. Additionally, the HFS can measure heat flux in both exothermic and absorptive cases and can measure heat flux up to 25 kW/m2. Additionally, we demonstrate the application of the HFS to the measurement of minuscule heat flux, such as heat dissipation of human skin and cold water. This technology is expected to be used in heat flux measurements at ultralow temperatures or on complex surfaces, which has great importance in the superconductor and cryobiology field.

Abstract Karst World Heritage Site (KWHS) combines high-grade landscape resources and a fragile ecological environment. As an essential tool for heritage conservation and maintaining local interests, its buffer zone is primarily located in remote villages, a crucial and challenging area for rural revitalization. The conflict between heritage conservation and development is particularly acute at the site. How to deal with the relationship between the heritage site’s OUV conservation and the buffer zone's tourism industry development and realize the synergy between the two subsystems? Few studies have focused on it. There is an urgent need to explore the synergistic mechanism of the KWHS's OUV conservation and the buffer zone's tourism industry development. Accordingly, this study takes the Libo-Huanjiang KWHS, one of the 'South China Karst' series of heritage sites, as a case study. The coupling coordination degree model, gray correlation analysis (GCA), and Geographic Information System (GIS) spatial analysis are used. The results show that: (1) There is a synergistic effect between the Libo-Huanjiang KWHS's OUV conservation and its buffer zone's tourism industry development, showing a favorable trend. The mean value of the coupling coordination degree increased from 0.57 in 2015 to 0.63 in 2020, and the overall situation improved from barely coupling coordination state to primary coupling coordination. (2) Influenced by the main driving factors, such as NDVI, landscape dominance, government support for tourism development, tourists' satisfaction, and residents' support, the coupling coordination of the four tourist scenic areas in the study area differed slightly in 2015 and 2020. Yaoshan Ancient Village Scenic Area is the highest in both years, increasing from 0.69 to 0.81, followed by the Mengliu Buyi Scenic Area (0.59), Wanmu Meiyuan Scenic Area is relatively stable with a slight increase, and Lianshanwan Scenic Area (0.45) is the lowest. (3) The four dimensions of ecological resources, policy drivers, economy drivers, and social facilitators work together to create a synergistic mechanism between the KWHS's OUV conservation and the buffer zone's tourism industry development. Future research can promote synergy between the two by formulating a comprehensive plan, encouraging sustainable tourism, establishing a diversified tourism industry, strengthening heritage education and training, enhancing community participation, and reinforcing stakeholder cooperation.

China has abundant oil shale resources and in-situ conversion is necessary for the large-scale, efficient and environmentally friendly development of this source rock. Despite the numerous researches carried out on in-situ transformation, reservoir reconstruction and heating technology, there is a lack of selection and evaluation criteria for high-quality mining areas. Therefore, it is urgent to perform geological evaluation and selection of favourable target areas for the in-situ conversion of oil shale-bearing areas in continental basins in China. In this paper, based on a wealth of research and previous studies, the geological characteristics of oil shale deposits in Chinaâs continental basins are studied. The in-situ conversion of oil shale mainly depends on the quality of rock, deposit characteristics, resource amount and hydrological conditions for site selection. On this basis, geological parameters, such as oil yield, organic matter type and maturity, ore body thickness, stratum dip angle, tectonics, lithology of the oil shale body roof and floor, oil shale resources and water content, are further considered. In addition, in conformity with the factor product method, the comprehensive geological parameters of each mining area are obtained and sorted according to a weighting coefficient. The preliminary results reveal that the Fushun and Bagemaode mining areas are two first-class favourable target areas. Gaozhou, Maoming, Fuyu-Changchun Ridge and eight other mining areas are second-class, less favourable target areas, while 16 future alternative areas include Tongchuan, Qidaoquanzi, Tanshanling, etc.

Infrared ship detection is of great significance due to its broad applicability in maritime surveillance, traffic safety and security. Multiple infrared sensors with different spectral sensitivity provide enhanced sensing capabilities, facilitating ship detection in complex environments. Nevertheless, current researches lack discussion and exploration of infrared imagers in different spectral ranges for marine objects detection. Furthermore, for unmanned marine vehicles (UMVs), e.g., unmanned surface vehicles (USVs) and unmanned ship (USs), detection and perception are usually performed in embedded devices with limited memory and computation resource, which makes traditional convolutional neural network (CNN)-based detection methods struggle to leverage their advantages. Aimed at the task of sea surface object detection on USVs, this paper provides lightweight CNNs with high inference speed that can be deployed on embedded devices. It also discusses the advantages and disadvantages of using different sensors in marine object detection, providing a reference for the perception and decision-making modules of USVs. The proposed method can detect ships in short-wave infrared (SWIR), long-wave infrared (LWIR) and fused images with high-performance and high-inference speed on an embedded device. Specifically, the backbone is built from bottleneck depth-separable convolution with residuals. Generating redundant feature maps by using cheap linear operation in neck and head networks. The learning and representation capacities of the network are promoted by introducing the channel and spatial attention, redesigning the sizes of anchor boxes. Comparative experiments are conducted on the infrared ship dataset that we have released which contains SWIR, LWIR and the fused images. The results indicate that the proposed method can achieve high accuracy but with fewer parameters, and the inference speed is nearly 60 frames per second (FPS) on an embedded device.

Abstract Background Delayed neutrophil apoptosis during sepsis may impact neutrophil organ accumulation and tissue immune homeostasis. Elucidating the mechanisms underlying neutrophil apoptosis may help identify potential therapeutic targets. Glycolysis is critical to neutrophil activities during sepsis. However, the precise mechanisms through which glycolysis regulates neutrophil physiology remain under-explored, especially those involving the non-metabolic functions of glycolytic enzymes. In the present study, the impact of programmed death ligand-1 (PD-L1) on neutrophil apoptosis was explored. The regulatory effect of the glycolytic enzyme, pyruvate kinase M2 (PKM2), whose role in septic neutrophils remains unaddressed, on neutrophil PD-L1 expression was also explored. Methods Peripheral blood neutrophils were isolated from patients with sepsis and healthy controls. PD-L1 and PKM2 levels were determined by flow cytometry and Western blotting, respectively. Dimethyl sulfoxide (DMSO)-differentiated HL-60 cells were stimulated with lipopolysaccharide (LPS) as an in vitro simulation of septic neutrophils. Cell apoptosis was assessed by annexin V/propidium iodide (annexin V/PI) staining, as well as determination of protein levels of cleaved caspase-3 and myeloid cell leukemia-1 (Mcl-1) by Western blotting. An in vivo model of sepsis was constructed by intraperitoneal injection of LPS (5 mg/kg) for 16 h. Pulmonary and hepatic neutrophil infiltration was assessed by flow cytometry or immunohistochemistry. Results PD-L1 level was elevated on neutrophils under septic conditions. Administration of neutralizing antibodies against PD-L1 partially reversed the inhibitory effect of LPS on neutrophil apoptosis. Neutrophil infiltration into the lung and liver was also reduced in PD-L1−/− mice 16 h after sepsis induction. PKM2 was upregulated in septic neutrophils and promoted neutrophil PD-L1 expression both in vitro and in vivo. In addition, PKM2 nuclear translocation was increased after LPS stimulation, which promoted PD-L1 expression by directly interacting with and activating signal transducer and activator of transcription 1 (STAT1). Inhibition of PKM2 activity or STAT1 activation also led to increased neutrophil apoptosis. Conclusion In this study, a PKM2/STAT1-mediated upregulation of PD-L1 on neutrophils and the anti-apoptotic effect of upregulated PD-L1 on neutrophils during sepsis were identified, which may result in increased pulmonary and hepatic neutrophil accumulation. These findings suggest that PKM2 and PD-L1 could serve as potential therapeutic targets.

Abstract Metastable noble metal nanocrystals may exhibit distinctive catalytic properties to address the sluggish kinetics of many important processes, including the hydrogen evolution reaction under alkaline conditions for water-electrolysis hydrogen production. However, the exploration of metastable noble metal nanocrystals is still in its infancy and suffers from a lack of sufficient synthesis and electronic engineering strategies to fully stimulate their potential in catalysis. In this paper, we report a synthesis of metastable hexagonal Pt nanostructures by coherent growth on 3d transition metal nanocrystals such as Ni without involving galvanic replacement reaction, which expands the frontier of the phase-replication synthesis. Unlike noble metal substrates, the 3d transition metal substrate owns more crystal phases and lower cost and endows the hexagonal Pt skin with substantial compressive strains and programmable charge density, making the electronic properties particularly preferred for the alkaline hydrogen evolution reaction. The energy barriers are greatly reduced, pushing the activity to 133 mA cmgeo –2 and 17.4 mA μgPt –1 at –70 mV with 1.5 µg of Pt in 1 M KOH. Our strategy paves the way for metastable noble metal catalysts with tailored electronic properties for highly efficient and cost-effective energy conversion.

Abstract Background The prevalence of multidrug-resistant hypervirulent K. pneumoniae (MDR-hvKP) has gradually increased. It poses a severe threat to human health. However, polymyxin-resistant hvKP is rare. Here, we collected eight polymyxin B-resistant K. pneumoniae isolates from a Chinese teaching hospital as a suspected outbreak. Results The minimum inhibitory concentrations (MICs) were determined by the broth microdilution method. HvKP was identified by detecting virulence-related genes and using a Galleria mellonella infection model. Their resistance to serum, growth, biofilm formation, and plasmid conjugation were analyzed in this study. Molecular characteristics were analyzed using whole-genome sequencing (WGS) and mutations of chromosome-mediated two-component systems pmrAB and phoPQ, and the negative phoPQ regulator mgrB to cause polymyxin B (PB) resistance were screened. All isolates were resistant to polymyxin B and sensitive to tigecycline; four were resistant to ceftazidime/avibactam. Except for KP16 (a newly discovered ST5254), all were of the K64 capsular serotype and belonged to ST11. Four strains co-harbored bla KPC-2, bla NDM-1, and the virulence-related genes p rmpA, p rmpA2, iucA, and peg344, and were confirmed to be hypervirulent by the G. mellonella infection model. According to WGS analysis, three hvKP strains showed evidence of clonal transmission (8–20 single nucleotide polymorphisms) and had a highly transferable pKOX_NDM1-like plasmid. KP25 had multiple plasmids carrying bla KPC-2, bla NDM-1, bla SHV-12, bla LAP-2, tet(A), fosA5, and a pLVPK-like virulence plasmid. Tn1722 and multiple additional insert sequence-mediated transpositions were observed. Mutations in chromosomal genes phoQ and pmrB, and insertion mutations in mgrB were major causes of PB resistance. Conclusions Polymyxin-resistant hvKP has become an essential new superbug prevalent in China, posing a serious challenge to public health. Its epidemic transmission characteristics and mechanisms of resistance and virulence deserve attention.

We propose a multimode fiber laser sensor utilizing PI-SMF (polyimide-coated single mode fiber) for low-error relative humidity (RH) measurement, which is temperature compensated based on FBG. The PI-SMF in the laser cavity is used as a sensing element, and its length varies with humidity and temperature by volume-variation induced strain, which leads to frequency shift of the longitudinal mode beat frequency signal (BFS). When the 2000 MHz BFS is selected as the sensing signal, a RH sensitivity of −2.68 kHz/%RH and a temperature sensitivity of −14.05 kHz/°C are achieved. The peak shift of the FBG-based laser emission spectrum is only sensitive to temperature rather than RH with a temperature sensitivity of 9.95 pm/°C, which is used as the temperature compensation for RH measurements. By monitoring the response of the BFS and the laser wavelength, the cross-sensitivity effect of RH and temperature is overcome, and low-error RH measurement in the temperature range of 20 to 65 °C is realized with errors within ±0.67 %RH (25 to 85 %RH). The scheme does not require the design and production of complex structures and hygroscopic material coating processes, owning the advantages of simple structure, easy operation and high accuracy, and is expected to be practically applied in food safety and environmental monitoring.

While water-splitting electrolysis offers a potential renewable means to store energy, the oxygen evolution half-reaction’s sluggish kinetics limits performances. Here, authors incorporation boron into nickel-iron hydroxide catalysts to promote electrocatalytic water oxidation activities

Summary: Flexible thin-film thermocouples (TFTCs) have been garnering interest as temperature sensors due to the advantages of being flexible, ultrathin, and ultralight. Additionally, they have fast response times and enable detection of temperature. These properties have made them suitable for applications such as wearable electronics, healthcare, portable personal devices, and smart detection systems. This review presents the progress in the development of flexible TFTCs. The mechanism, structural design, materials, fabrication methods, and related applications of flexible TFTCs are also elaborated. Finally, future development directions of flexible TFTCs are discussed such as wide-range temperature measurement, multiple sensor integration, and achieving reliable cold-end compensation systems.

Non-alcoholic fatty liver disease (NAFLD) has a global prevalence of approximately 25 % and is associated with high morbidity and high mortality. NAFLD is a leading cause of cirrhosis and hepatocellular carcinoma. Its pathophysiology is complex and still poorly understood, and there are no drugs used in the clinic to specifically treat NAFLD. Its pathogenesis involves the accumulation of excess lipids in the liver, leading to lipid metabolism disorders and inflammation. Phytochemicals with the potential to prevent or treat excess lipid accumulation have recently received increasing attention, as they are potentially more suitable for long-term use than are traditional therapeutic compounds. In this review, we summarize the classification, biochemical properties, and biological functions of flavonoids and how they are used in the treatment of NAFLD. Highlighting the roles and pharmacological uses of these compounds will be of importance for enhancing the prevention and treatment of NAFLD.

High-temperature thin-film thermocouples (TFTCs) have attracted significant attention in the aerospace and steel metallurgy industry. However, previous studies on TFTCs have primarily focused on the two-dimensional planar-type, whose thermal sensitive area has to be perpendicular to the test environment, and therefore affects the thermal fluids pattern or loses accuracy. In order to address this problem, recent studies have developed three-dimensional probe-type TFTCs, which can be set parallel to the test environment. Nevertheless, the probe-type TFTCs are limited by their measurement threshold and poor stability at high temperatures. To address these issues, in this study, we propose a novel probe-type TFTC with a sandwich structure. The sensitive layer is compounded with indium oxide doped zinc oxide and fabricated using screen-printing technology. With the protection of sandwich structure on electrode film, the sensor demonstrates robust high-temperature stability, enabling continuous working at 1200 °C above 5 h with a low drift rate of 2.3 °C·h ^−1 . This sensor exhibits a high repeatability of 99.3% when measuring a wide range of temperatures, which is beyond the most existing probe-type TFTCs reported in the literature. With its excellent high-temperature performance, this temperature sensor holds immense potentials for enhancing equipment safety in the aerospace engineering and ensuring product quality in the steel metallurgy industry.

Abstract In recent decades, World Heritage Sites (WHSs) have faced external severe threats in the context of global economisation and urbanisation. The buffer zone as a conservation layer and management tool for WHSs has attracted increasing scholarly attention and debate. However, there is limited understanding of buffer zones’ social and ecological role in the conservation of World Natural Heritage Sites (WNHSs) and a lack of summary of research progress on buffer zones. To fill this gap, this study systematically reviews the existing knowledge and research gaps on buffer zones in WNHSs worldwide. We used a systematic literature review framework of Search, Assessment, Synthesis and Analysis (SALSA) through the WoS and CNKI databases to obtain 188 articles that met the inclusion criteria. The aim was to analyze the temporal and regional distribution of publications, types of studies, main processes and landmark achievements, gaps, and implications for future research. Results indicated that: (1) there is an overall upward trend in the number of publications, reaching a maximum in 2020, with the most published in Asia and Europe. The research process presents two main categories of ecologically and socially oriented. (2) The main landmark achievements include theoretical research, technology and methods, model construction, benefit monitoring and evaluation, experimental demonstration, etc. Among them, theoretical research is the most numerous (58.51%). (3) On this basis, 8 key scientific issues are summarised. Reviewing the research progress and summarising the critical scientific issues will provide practical guidance for the effective implementation of the role of buffer zones in global WNH conservation, especially for karst WNHSs with fragile ecological environments. (4) The future of Karst WNH conservation should be based on the effect of human-land relationship in promoting heritage protection. Examining the institutional factors of ecological problems and the management of degraded ecosystems from a socio-economic perspective. The purpose is to seek a socio-ecological system that is composed of the social, economic, ecological and cultural dimensions of the buffer zone. Focus on the coupling between eco-industrial development and WNH conservation, and strengthen buffer zone communities’ adaptive and collaborative management. Explore techniques and methods of conservation adapted to the characteristics of the fragile ecosystem of karst itself, and conduct experimental demonstrations.

Macrobenthic bioturbation affects the environment, and variances in habitat, such as decreased dissolved oxygen concentration and increased ammonia concentration, affects the macrobenthic community. The relationship between macrobenthos and habitat factors may be a mutually causal relationship. The bottom-sowing culture for Manila clam Ruditapes philippinarum in many coastal countries plays an important role in coastal fisheries, and the relationship between Manila clam and other macrobenthos affects the ecological stability of the bottom-sowing culture zone. It is necessary to explore the relationship between them to manage the waters used for the bottom-sowing culture for Manila clam. In this study , from June to October 2021, the field investigation on macrobenthos including Manila clam and their habitat factors, such as particle size, nutrient content, redox potential, and organic matter content, in 21 experimental communities enclosed by bolting-silk net in Shuangdao Bay, Weihai, Shandong, China was conducted, during which macrobenthos functional groups were determined by feed sources and motor behavior. The results showed that Manila clam biomass was 7.215±0.984 g/m2 (calculated by dry soft tissue weight), and it was positively correlated with the biomass of macrobebthos functional groups B1, G1 and P1; water content in sediment; sulfide content in interstitial water; the Shanon-Wiener diversity index; Pielou’s evenness index and the W statistic of the ABC (Abundance-Biomass Comparison) curve (p< 0.05). Moreover, it was negatively correlated with sediment particulate size and HCl-NO3 content in sediment (p< 0.05). The action of Manila clam to habitats was the dominant role of the interaction between clam and habitat. Thus, the bottom-sowing culture for Manila clam does not decrease the macrobenthic community stability, and the invasion of other macrobenthos into the bottom-sowing culture zones for Manila clam may be accidental or inevitable. The results of our study suggest that the management of the bottom-sowing culture for Manila clam should be conducted from ecosystem level; i.e., fishing and aquaculture in the same waters are regarded as two components of an ecosystem; manage them together, rather than treat them separately.

Abstract In the context of integrating culture and tourism, world heritage tourism research has become a focus in tourism research in recent years. There are increasing discussions in academic circles on the content and methods of this field. Clarifying the knowledge system of research is conducive to dialogue with international theoretical frontiers and integrating, analyzing, and predicting the progress and lineage from a more comprehensive perspective. Still, few studies on the knowledge system of world heritage tourism research have been conducted. To fill this gap, this study uses the SSCI and SCI sub-databases of Web of Science Core Collection as the data source with the help of CiteSpace and VOSviewer software to measure the knowledge system of world heritage tourism research. A bibliometric analysis of 567 publications between 1992 and 2020 was conducted to construct a framework of a knowledge system based on literature statistics and content analysis, revealing the geographic research regions, theories and methods, themes and contents, trend evolution, and future research inspiration. The results show that: (1) the number of publications tends to increase gradually, with the highest in 2019. The authors and research institutions are mainly concentrated in Europe, America, East Asia. China has the highest publications. More literature on cultural heritage as a geographical study area than natural heritage. (2) The research themes, objects, and methods of the sample literature have become more diversified with the advancement of the research stage. The literature on multi-stakeholder research is the largest, followed by tourism impacts and research on World Heritage Sites’ resource management techniques and methods. These studies provide a multifaceted interpretation of the sustainable development of World heritage tourism, mainly from the perspectives of both supply and demand. However, the theoretical system is still incomplete. (3) Future research should strengthen the theoretical system construction, research innovation, cooperation, and research exchange in world heritage tourism research. Pay more attention to the research on the pluralistic value system of world heritage. Focus on exploring research on world heritage tourism’s resilience and localization dilemmas under the impact of the New Crown epidemic. To reveal the synergistic mechanisms and paths of diversified livelihoods of World Heritage Sites’ residents in ecologically fragile and impoverished areas.

In order to improve the signal-to-noise ratio (SNR) of vibration sensing in the phase-sensitive optical time-domain reflectometer (φ-OTDR) system, a fiber sensing signal processing method based on the FFDNet convolutional neural network is proposed in this paper. In the network, the concept of residual learning is introduced, which involves constructing a residual mapping and utilizing multi-layer convolutional neural networks to learn the noise distribution present in the original image. The denoised result can be obtained by subtracting the learned noise from the original image. We have built a φ-OTDR system based on coherent detection, using three PZTs as simulated vibration sources and a series of experiments at 200 Hz, with each experiment simulating a single vibration event or multiple vibration events by setting different intensities. The experimental results demonstrate that the FFDNet based fiber optic sensing signal processing method enhances the SNR to 37.84 dB, 37.11 dB, and 37.31 dB, respectively, while preserving vibration signal details more effectively than wavelet denoising and Gaussian filtering techniques. The trained FFDNet model has great potential for improving the performance of the φ-OTDR system and has some practical application value.

Numerous studies have established that the hypoxic conditions within ovarian follicles induce apoptosis in granulosa cells (GCs), a pivotal hallmark of follicular atresia. Melatonin (N-acetyl-5-methoxytryptamine, MT), a versatile antioxidant naturally present in follicular fluid, acts as a safeguard for maintaining GCs’ survival during stress exposure. In this study, we unveil an innovative protective mechanism of melatonin against hypoxia-triggered GC apoptosis by selectively inhibiting mitochondrial ROS (mtROS) generation. Specifically, under hypoxic conditions, a gradual accumulation of mitochondrial ROS occurred, consequently activating the JNK-FOXO1 pathway, and driving GCs toward apoptosis. The blocking of JNK or FOXO1 diminished hypoxia-induced GC apoptosis, but this effect was nullified in the presence of GSH, indicating that mtROS instigates apoptosis through the JNK-FOXO1 pathway. Consistent with this, hypoxic GCs treated with melatonin exhibited decreased levels of mtROS, reduced JNK-FOXO1 activation, and mitigated apoptosis. However, the protective capabilities of melatonin were attenuated upon inhibiting its receptor MTNR1B, accompanied by the decreased expression of antioxidant genes. Notably, SOD2, a key mitochondrial antioxidant gene modulated by the melatonin–MTNR1B axis, effectively inhibited the activation of mtROS-JNK-FOXO1 and subsequent apoptosis, whereas SOD2 knockdown abrogated the protective role of melatonin in hypoxic GCs. In conclusion, our study elucidates that melatonin, through MTNR1B activation, fosters SOD2 expression, effectively quelling mtROS-JNK-FOXO1-mediated apoptosis in follicular GCs under hypoxic stress.

The tomb of Hanxiu, a prime minister of the Tang dynasty who died in 740 CE, was decorated with elaborate mural paintings. The pigments used in the mural paintings were collected from representative colours before a restoration process and analyzed using micro-Raman and scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM-EDS) analysis to characterize the chemical compositions. The results reveal the chromatic palette and the painting technique used in the mural paintings. Most of the pigments are natural mineral pigments similar to those excavated in previous archaeological works, except the yellow pigment is unusual. A rare mineral pigment, vanadinite [Pb5(VO4)3Cl], was employed in a large amount as the yellow pigment. This phenomenon was analyzed and compared with tomb mural paintings from varied periods and locations in ancient China. Notably, the identification of vanadinite via Raman spectra has to be performed carefully and combined with an elemental analysis to avoid misidentification.

Abstract Aim To explore the effect of TEC chemotherapy regimen (Docetaxel + Epirubicin + Cyclophosphamide) on traditional cardiovascular risk factors, atherosclerotic cardiovascular disease and cardiac electrical activity. Design 243 patients with first initially diagnosed breast cancer were collected who receiving TEC chemotherapy. Methods Univariate analysis, multivariate analysis, binary logistic regression analysis and statistical description were used to analyse the data. Results Among the first diagnosed patients, prevalence of hypertension and overweight/obesity in postmenopausal patients were significantly higher than premenopausal group. Compared with initially diagnosed state, incidence of hyperlipidaemia increased significantly after TEC chemotherapy, blood glucose level was remarkably increased, and prevalence of hyperuricaemia was significantly increased, changes of blood pressure level and prevalence rate of hypertension were not significant, and there was no statistical difference. Different menopause status showed the same trend. Atherosclerotic cardiovascular disease risk stratification showed after chemotherapy low‐risk patients decrease, medium‐risk and high‐risk people increased. Grouped by menstrual status, after chemotherapy, both groups showed the same trend. The independent influencing factors of increased heart rate after chemotherapy were postmenopausal status. Postmenopausal patients had more cardiovascular risk factors than premenopausal patients. After receiving chemotherapy, levels of cardiovascular risk factors in both groups mostly changed to the direction of disease. Chemotherapy drugs increase the risk of atherosclerotic cardiovascular disease in breast cancer patients. It is necessary to strengthen interdisciplinary cooperation to dynamic assess the cardiovascular health of patients of breast cancer patients.

Abstract Background Effective removal of pathogenic bacteria is key to improving the prognosis of sepsis. Polymorphonuclear neutrophils (PMNs) are the most important components of innate cellular immunity and play vital roles in clearing pathogenic bacteria. However, the metabolic characteristics and immunomodulatory pathways of PMNs during sepsis have not been investigated. In the present study, we explored the immune metabolism characteristics of PMNs and the mechanism by which neutrophilic glycolysis is regulated during sepsis. Methods Metabolomics analysis was performed on PMNs isolated from 14 septic patients, 26 patients with acute appendicitis, and 19 healthy volunteers. Transcriptome analysis was performed on the PMNs isolated from the healthy volunteers and the patients with sepsis to assess glycolysis and investigate its mechanism. Lipopolysaccharide (LPS) was used to stimulate the neutrophils isolated from the healthy volunteers at different time intervals to build an LPS-tolerant model. Chemotaxis, phagocytosis, lactate production, oxygen consumption rate (OCR), and extracellular acidification rate (ECAR) were evaluated. Results Transcriptomics showed significant changes in glycolysis and the mTOR/HIF-1α signaling pathway during sepsis. Metabolomics revealed that the Warburg effect was significantly altered in the patients with sepsis. We discovered that glycolysis regulated PMNs’ chemotaxis and phagocytosis functions during sepsis. Lactate dehydrogenase A (LDHA) downregulation was a key factor in the inhibition of glycolysis in PMNs. This study confirmed that the PI3K/Akt-HIF-1α pathway was involved in the LDHA expression level and also influenced PMNs’ chemotaxis and phagocytosis functions. Conclusions The inhibition of glycolysis contributed to neutrophil immunosuppression during sepsis and might be controlled by PI3K/Akt-HIF-1α pathway-mediated LDHA downregulation. Our study provides a scientific theoretical basis for the management and treatment of patients with sepsis and promotes to identify therapeutic target for the improvement of immune function in sepsis.

Seed germination is an essential biological process for establishing new organisms of higher plants, it is especially significant for those aged seeds stored in gene banks for years. In this study, we investigated ultrasound treatment induced germination for aged Pinus tabuliformis seeds, which has been used in large scale aircraft sowing based afforestation in North China over 30 years’ ago without knowing possible mechanisms. We showed certain strength of ultrasound could increase the germination rate of aged seeds for about 3 times compare with control. Interestingly, although our transcriptome and lipidome analysis showed the differences between control and ultrasound treatments can be observed 1 day after germination by partial least squares discriminant analysis (PLSDA) analysis, majority (75 % or 69 %) of the significantly altered genes or lipids were commonly shared between them. Further analysis for the commonly altered lipids between both treatments showed ultrasound provoked the variations of lipids during germination process. Our investigation also revealed large amount of ultrasound-related genes and lipids that might be involved in germination promotion process. We hypothesis ultrasound provokes seed lipidome which further increases seed germination of Pinus tabuliformis. Our study provides new insides into the role of ultrasound induced lipidome change in seed germination. Moreover, we provide a new method to improve germination of aged seeds which might benefit preservation of seeds in gene banks.

BackgroundA feasible method to detect somatic copy number deletion (SCND) of genes is still absent to date.MethodsInterstitial base-resolution deletion/fusion coordinates for CDKN2A were extracted from published articles and our whole genome sequencing (WGS) datasets. The copy number of the CDKN2A gene was measured with a quantitative multiplex PCR assay P16-Light and confirmed with whole genome sequencing (WGS).ResultsEstimated common deletion regions (CDRs) were observed in many tumor suppressor genes, such as ATM, CDKN2A, FAT1, miR31HG, PTEN, and RB1, in the SNP array-based COSMIC datasets. A 5.1 kb base-resolution CDR could be identified in >90% of cancer samples with CDKN2A deletion by sequencing. The CDKN2A CDR covers exon-2, which is essential for P16INK4A and P14ARF synthesis. Using the true CDKN2A CDR as a PCR target, a quantitative multiplex PCR assay P16-Light was programmed to detect CDKN2A gene copy number. P16-Light was further confirmed with WGS as the gold standard among cancer tissue samples from 139 patients.ConclusionThe 5.1 kb CDKN2A CDR was found in >90% of cancers containing CDKN2A deletion. The CDKN2A CDR was used as a potential target for developing the P16-Light assay to detect CDKN2A SCND and amplification for routine clinical practices.

White-light scanning interferometry (WLSI) is a mature and efficient technique that is widely used in the field of high-precision three-dimensional measurements. However, coherence and phase information in the WLSI technique are inconsistent, false height jumps, such as batwings artifact and ghost steps, are typical obstacles in applying WLSI, which distort measurement results and reduce the measurement accuracy. In this study, we proposed a composite wavelet decomposition algorithm combined with a correlation analysis to solve the above two obstacles without having any prior knowledge about the tested sample. Two calibration step plates with heights of 459.8 ± 3.0 nm and 90.5 ± 2.8 nm were used to evaluate the accuracy of the proposed algorithm, and the results were compared with those of Centroid and Fourier transform algorithms. Consequently, the proposed algorithm exhibited a higher correction effect, and the accuracy was improved by more than two times, which proved that our approach could effectively suppress the batwings effect and eliminate the ghost steps.

Non-alcoholic fatty liver disease (NAFLD) is a public health problem associated with high mortality and high morbidity rates worldwide. Presently, its complex pathophysiology is still unclear, and there is no specific drug to reverse NAFLD. Ferroptosis is an iron-dependent and non-apoptotic form of cell death characterized by the iron-induced accumulation of lipid reactive oxygen species (ROS), which damage nucleic acids, proteins, and lipids; generate intracellular oxidative stress; and ultimately cause cell death. Emerging evidence indicates that ferroptosis is involved in the progression of NAFLD, although the mechanism of action of ferroptosis in NAFLD is still poorly understood. Herein, we summarize the mechanism of action of ferroptosis in certain diseases, especially in the pathogenesis of NAFLD, and discuss the potential therapeutic approaches currently used to treat NAFLD. This review also highlights further directions for the treatment and prevention of NAFLD and related diseases.

This work explores the pivotal role of laser lift-off (LLO) as a vital production process in facilitating the integration of Micro-LEDs into display modules. We specifically investigate the LLO process applied to high-performance gallium nitride (GaN)-based green Micro-LED arrays, featuring a pixel size of 20 × 38 μm on a patterned sapphire substrate (PSS). Scanning electron microscopy (SEM) observations demonstrate the preservation of the GaN film and sapphire substrate, with no discernible damage. We conduct a comprehensive analysis of the optoelectrical properties of the Micro-LEDs both before and after the LLO process, revealing significant enhancements in light output power (LOP) and external quantum efficiency (EQE). These improvements are attributed to more effective light extraction from the remaining patterns on the GaN backside surface. Furthermore, we examine the electroluminescence spectra of the Micro-LEDs under varying current conditions, revealing a slight change in peak wavelength and an approximate 10% decrease in the full width at half maximum (FWHM), indicating improved color purity. The current–voltage (I–V) curves obtained demonstrate the unchanged forward voltage at 2.17 V after the LLO process. Our findings emphasize the efficacy of LLO in optimizing the performance and color quality of Micro-LEDs, showcasing their potential for seamless integration into advanced display technologies.

Abstract Objective We aimed to explore the cardiovascular characteristics of patients who were initially diagnosed with breast cancer. Methods A total of 600 patients who were diagnosed with primary breast cancer were included in this retrospective study. The data of fasting blood glucose, total cholesterol, total triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, lipoprotein (a) (LP (a)) and serum uric acid were collected. Univariate analysis was used to evaluate the cardiovascular risk factors (CVRFs) in patients with breast cancer. The arteriosclerotic cardiovascular disease (ASCVD) risk assessment was performed. Multivariate analysis was used to identify the factors that influenced axillary lymph node metastasis (ALNM). Results Compared with the premenopausal group, the prevalence of overweight/obesity (47.6% vs. 35.2%), diabetes (12.8% vs. 4.3%) and hypertension (49.7% vs. 26.3%) were significantly increased in the postmenopausal group (p

Abstract Accurate temperature measurements can efficiently solve numerous critical problems and provide key information. Herein, a flexible micro-three-dimensional sensor, with a combination of platinum and indium oxide to form thermocouples, is designed and fabricated by a microfabrication process to achieve in situ real-time temperature measurements. The stability and reliability of the sensor are greatly improved by optimizing the process parameters, structural design, and preparation methods. A novel micro-three-dimensional structure with better malleability is designed, which also takes advantage of the fast response of a two-dimensional thin film. The as-obtained flexible temperature sensor with excellent stability and reliability is expected to greatly contribute to the development of essential components in various emerging research fields, including bio-robot and healthcare systems. The model of the application sensor in a mask is further proposed and designed to realize the collection of health information, reducing the number of deaths caused by the lack of timely detection and treatment of patients.

Despite being a significant public health concern, hypervirulent Klebsiella pneumoniae (hvKP) has rarely been investigated in urinary tract infections (UTIs). To investigate the molecular and clinical characterization of hvKP in UTIs, we collected K. pneumoniae strains and clinical data from patients with UTIs. HvKP was confirmed by virulence-related genes and the Galleria mellonella model and sequenced by next-generation sequencing. Our data showed that 30/121 isolates were hvKP [17 carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP), 12 hvKP, and 1 extended-spectrum β-lactamase-producing hvKP]; these had higher resistance to most antimicrobials and were more likely to cause complicated UTIs (cUTIs). Notably, the mucoid phenotype-regulating genes prmpA and prmpA2 were truncated in 3 and 19 hvKP, respectively. Eight serotypes were detected and divided into three groups: K64 (n = 17), K1/K2 (n = 6), and others (n = 7). Furthermore, 16/17 K64 hvKP isolates were CR-hvKP but with a lower mortality rate of G. mellonella as the truncated prmpA/prmpA2 incurred high fitness cost to the isolates. In addition, all K64 isolates belonged to ST11 with the same cluster, and in two of these strains (KP88 and KP92) blaKPC-2 gene was successfully transferred to EC600. Genetic environment analysis showed that IS26–tnpR–ISKpn27–blaKPC−2–ISKpn6 may be the core structure in the horizontal transfer of blaKPC-2. The highest mortality rate among the infected G. mellonella was observed in the K1/K2 group. In conclusion, hvKP had a higher resistance rate and was more likely to lead to cUTIs. Convergence of hypervirulence and carbapenem resistance in a transmissible ST11 clone of K64 K. pneumoniae was mediated by a plasmid in UTIs. Therefore, surveillance of hvKP in UTIs should be strengthened.

Acinetobacter baumannii (AB) infection has become a threat to global public health. AB is one of the main pathogens causing nosocomial infections, especially ventilator-associated pneumonia. AB easily develops resistance against a variety of antibiotics, which makes the treatment of AB infections difficult. Therefore, it is necessary to study new treatment plans like anti-infection immunity. Both animal models of AB infection and in vitro cell experiments show that macrophages are activated in the early stage of the immune response and regulate the recruitment of neutrophils, thus playing a role in clearing AB. AB components and the immune responses they induce can lead to injury of the infected organ, mostly in the lungs. Understanding the response of innate immunity to ABs at different stages after infection and the relationship between the response and lung injury can help to develop new immunotherapy methods and prevent lung injury. This article provides a comprehensive review of the response of neutrophils and macrophages to AB infection and their association with lung injury to develop effective therapies for AB infection and prevent lung injury.

A frequency comb generator (FCG) based on dual-cavity Brillouin random fiber lasing oscillation in the 1.5 μm telecon spectral window is established and experimentally demonstrated. In the half-open main cavity of the dual cavity, the stimulated Brillouin scattering in highly nonlinear fiber (HNLF) and Rayleigh scattering in single-mode fiber are employed to provide sufficient Brillouin gain and the randomly distributed feedback, respectively, for random mode resonance. The sub-cavity includes an Er-doped fiber amplifier to couple back and boost lower-order Stokes and anti-Stokes light for the cascade of stimulated Brillouin scattering to generate multiple higher-order Stokes and anti-Stokes light. Meanwhile, efficient four-wave mixing is stimulated in the HNLF-based main cavity, further enhancing the number and intensity of the resonant Stokes and anti-Stokes light. By taking advantages of the unique transmission characteristics of nonlinear optical loop mirrors, the power deviation between Stokes and anti-Stokes lines is further optimized with 17 orders of stable Stokes lines and 15 orders of stable anti-Stokes lines achieved within the 10 dB power deviation, with maximum optical signal-to-noise ratio (OSNR) of ~22 dB and ~17 dB and minimum OSNR of ~10 dB and ~7.5 dB for Stokes and anti-Stokes lines, respectively. In addition, the dynamic characteristics of the proposed FCG have been experimentally investigated. Such an FCG with fixed frequency spacing will find promising applications in fields of optical communication, microwave, optical sensing, etc.

This report investigated underwater wireless optical communication (UWOC) links in the presence of surface currents and tides. The scenario of surface currents and tides was generated by a sea water tank, a water pipe, and a water pump of different flow rates. It built the oceanic channel of UWOC varied with the salinity and flow rate in the UWOC transmission. The data rate of UWOC links based on a 520-nm laser diode and none-return-to-zero on-off keying (NRZ-OOK) modulation can achieve 3.4 Gb/s at a bit error rate (BER) of 3.78 $\times 10^{-4}$ in 1.8 m long sea water tank when a flow rate reached 1.08 m/s. The BER, eye-diagrams, and received signal optical power measurements showed that both the increasing salinity and flow rate cause the UWOC channel attenuation, thus degrade the performance of UWOC links.

Abstract Owing to high surface-to-volume ratio, InGaN-based micro-light-emitting diodes (μLEDs) strongly suffer from surface recombination that is induced by sidewall defects. Moreover, as the chip size decreases, the current spreading will be correspondingly enhanced, which therefore further limits the carrier injection and the external quantum efficiency (EQE). In this work, we suggest reducing the nonradiative recombination rate at sidewall defects by managing the current spreading effect. For that purpose, we properly reduce the vertical resistivity by decreasing the quantum barrier thickness so that the current is less horizontally spreaded to sidewall defects. As a result, much fewer carriers are consumed in the way of surface nonradiative recombination. Our calculated results demonstrate that the suppressed surface nonradiative recombination can better favor the hole injection efficiency. We also fabricate the μLEDs that are grown on Si substrates, and the measured results are consistent with the numerical calculations, such that the EQE for the proposed μLEDs with properly thin quantum barriers can be enhanced, thanks to the less current spreading effect and the decreased surface nonradiative recombination.

It is well established that 5-methylcytosine (5mC) in genomic DNA of mammalian cells can be oxidized into 5-hydroxymethylcytosine (5hmC) and other derivates by DNA dioxygenase TETs. While conversion of 5mC to 5hmC plays an important role in active DNA demethylation through further oxidation steps, a certain proportion of 5hmCs remain in the genome. Although 5hmCs contribute to the flexibility of chromatin and protect bivalent promoters from hypermethylation, the direct effect of 5hmCs on gene transcription is unknown. In this present study, we have engineered a zinc-finger protein-based P16-specific DNA dioxygenase (P16-TET) to induce P16 hydroxymethylation and demethylation in cancer cells. Our results demonstrate, for the first time, that although the hydroxymethylated P16 alleles retain transcriptionally inactive, hydroxymethylation could increase the susceptibility of reactivation of methylated P16 alleles.

Abstract Background There is a dearth of drug therapies available for the treatment of acute respiratory distress syndrome (ARDS). Certain metabolites play a key role in ARDS and could serve as potential targets for developing therapies against this respiratory disorder. The present study was designed to determine such “functional metabolites” in ARDS using metabolomics and in vivo experiments in a mouse model. Methods Metabolomic profiles of blood plasma from 42 ARDS patients and 28 healthy controls were captured using Ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) assay. Univariate and multivariate statistical analysis were performed on metabolomic profiles from blood plasma of ARDS patients and healthy controls to screen for “functional metabolites”, which were determined by variable importance in projection (VIP) scores and P value. Pathway analysis of all the metabolites was performed. The mouse model of ARDS was established to investigate the role of “functional metabolites” in the lung injury and mortality caused by the respiratory disorder. Results The metabolomic profiles of patients with ARDS were significantly different from healthy controls, difference was also observed between metabolomic profiles of the non-survivors and the survivors among the ARDS patient pool. Levels of Phenylalanine, D-Phenylalanine and Phenylacetylglutamine were significantly increased in non-survivors compared to the survivors of ARDS. Phenylalanine metabolism was the most notably altered pathway between the non-survivors and survivors of ARDS patients. In vivo animal experiments demonstrated that high levels of Phenylalanine might be associated with the severer lung injury and increased mortality of ARDS. Conclusion Increased mortality of acute respiratory distress syndrome was associated with high levels of plasma Phenylalanine. Trial registration Chinese Clinical Trial Registry, ChiCTR1800015930 . Registered 29 April 2018, http://www.chictr.org.cn/edit.aspx?pid=25609&htm=4

We propose a novel absolute calibrate method for digital holographic microscopy with the sequential shift method using Chebyshev polynomials. We separate the object phase and the aberrations by sequential shifting the sample twice in vertical plane of the optical axis. The aberrations phase is then calculated using the high order Chebyshev polynomials. The correct phase is obtained by subtracting the aberrations from the original phase containing the aberration. This method can compensate for the complex aberrations including high-order aberrations without changing the traditional optical system. Meanwhile, it can effectively protect the medium and high frequency information of the specimen in the phase image. Numerical simulation and experimental results demonstrate the availability and advantages of the absolute calibrate method.