Development of Highly Efficient Lamb Wave Transducers toward Dual-Surface Simultaneous Atomization.

Highly efficient surface acoustic wave (SAW) transducers offer significant advantages for microfluidic atomization. Aiming at highly efficient atomization, we innovatively accomplish dual-surface simultaneous atomization by strategically positioning the liquid supply outside the IDT aperture edge. Initially, we optimize Lamb wave transducers and specifically investigate their performance based on the ratio of substrate thickness to acoustic wavelength. When this ratio h/λ is approximately 1.25, the electromechanical coupling coefficient of A0-mode Lamb waves can reach around 5.5% for 128° Y-X LiNbO3. We then study the mechanism of droplet atomization with the liquid supply positioned outside the IDT aperture edge. Experimental results demonstrate that optimized Lamb wave transducers exhibit clear dual-surface simultaneous atomization. These transducers provide equivalent amplitude acoustic wave vibrations on both surfaces, causing the liquid thin film to accumulate at the edges of the dual-surface and form a continuous mist.

Adaptive Channel Allocation for Robust Differentiable Architecture Search.

Differentiable architecture search (DARTS) has attracted much attention due to its simplicity and significant improvement in efficiency. However, the excessive accumulation of the skip connection, when training epochs become large, makes it suffer from weak stability and low robustness, thus limiting its practical applications. Many works have attempted to restrict the accumulation of skip connections by indicators or manual design. These methods, however, are susceptible to human priors and hyperparameters. In this work, we suggest a more subtle and direct approach that no longer explicitly searches for skip connections in the search stage, based on the paradox that skip connections were proposed to guarantee the performance of very deep networks, but the networks in the search stage of DARTS are actually very shallow. Instead, by introducing channel importance ranking and channel allocation strategy, the skip connections are implicitly searched and automatically refilled unimportant channels in the evaluation stage. Our method, dubbed adaptive channel allocation (ACA) strategy, is a general-purpose approach for DARTS, which universally works in DARTS variants without introducing human priors, indicators, or hyperparameters. Extensive experiments on various datasets and DARTS variants verify that the ACA strategy is the most effective one among the existing methods in improving robustness and dealing with the collapse issue when training epochs become large.

Veillonella parvula promotes root caries development through interactions with Streptococcus mutans and Candida albicans.

Root caries is a subtype of dental caries that predominantly impacts older adults. The occurrence and progression of root caries are associated with the homeostasis of dental plaque biofilm, and microbial synergistic and antagonistic interactions in the biofilm play a significant role in maintaining the oral microecological balance. The objective of the current study was to investigate the role of Veillonella parvula in the microbial interactions and the pathogenesis of root caries. The analysis of clinical samples from patients with/without root caries revealed that Veillonella and V. parvula were abundant in the saliva of patients with root caries. More importantly, a significantly increased colonization of V. parvula was observed in root carious lesions. Further in vitro biofilm and animal study showed that V. parvula colonization increased the abundance and virulence of Streptococcus mutans and Candida albicans, leading to the formation of a polymicrobial biofilm with enhanced anti-stress capacity and cariogenicity, consequently exacerbating the severity of carious lesions. Our results indicate the critical role of V. parvula infection in the occurrence of root caries, providing a new insight for the etiological investigation and prevention of root caries.

Histidine Phosphorylation: Protein Kinases and Phosphatases.

Phosphohistidine (pHis) is a reversible protein post-translational modification (PTM) that is currently poorly understood. The P-N bond in pHis is heat and acid-sensitive, making it more challenging to study than the canonical phosphoamino acids pSer, pThr, and pTyr. As advancements in the development of tools to study pHis have been made, the roles of pHis in cells are slowly being revealed. To date, a handful of enzymes responsible for controlling this modification have been identified, including the histidine kinases NME1 and NME2, as well as the phosphohistidine phosphatases PHPT1, LHPP, and PGAM5. These tools have also identified the substrates of these enzymes, granting new insights into previously unknown regulatory mechanisms. Here, we discuss the cellular function of pHis and how it is regulated on known pHis-containing proteins, as well as cellular mechanisms that regulate the activity of the pHis kinases and phosphatases themselves. We further discuss the role of the pHis kinases and phosphatases as potential tumor promoters or suppressors. Finally, we give an overview of various tools and methods currently used to study pHis biology. Given their breadth of functions, unraveling the role of pHis in mammalian systems promises radical new insights into existing and unexplored areas of cell biology.

MAMs and Mitochondrial Quality Control: Overview and Their Role in Alzheimer's Disease.

Alzheimer's disease (AD) represents the most widespread neurodegenerative disorder, distinguished by a gradual onset and slow progression, presenting a substantial challenge to global public health. The mitochondrial-associated membrane (MAMs) functions as a crucial center for signal transduction and material transport between mitochondria and the endoplasmic reticulum, playing a pivotal role in various pathological mechanisms of AD. The dysregulation of mitochondrial quality control systems is considered a fundamental factor in the development of AD, leading to mitochondrial dysfunction and subsequent neurodegenerative events. Recent studies have emphasized the role of MAMs in regulating mitochondrial quality control. This review will delve into the molecular mechanisms underlying the imbalance in mitochondrial quality control in AD and provide a comprehensive overview of the role of MAMs in regulating mitochondrial quality control.

GMConv: Modulating Effective Receptive Fields for Convolutional Kernels.

In convolutional neural networks (CNNs), the convolutions are conventionally performed using a square kernel with a fixed N × N receptive field (RF). However, what matters most to the network is the effective receptive field (ERF), which indicates the extent to which input pixels contribute to an output pixel. Inspired by the property that ERFs typically exhibit a Gaussian distribution, we propose a Gaussian Mask convolutional kernel (GMConv). Specifically, GMConv utilizes the Gaussian function to generate a concentric symmetry mask that is placed over the kernel to refine the RF. We analyze the RFs of CNN kernels in different CNN layers and evaluate our approach through extensive experiments on image classification and object detection tasks. Over several tasks and standard base models, our approach compares favorably against the standard convolution. For instance, using GMConv for AlexNet and ResNet-50, the top-1 accuracy on ImageNet classification is boosted by 0.98% and 0.85% , respectively.

LHPP expression in triple-negative breast cancer promotes tumor growth and metastasis by modulating the tumor microenvironment.

Triple-negative breast cancer (TNBC) is a highly aggressive and metastatic form of breast cancer that lacks an effective targeted therapy. To identify new therapeutic targets, we investigated the phosphohistidine phosphatase, LHPP, which has been implicated in the development of several types of cancer. However, the full significance of LHPP in cancer progression remains unclear due to our limited understanding of its molecular mechanism. We found that levels of the LHPP phosphohistidine phosphatase were significantly increased in human breast cancer patients compared to normal adjacent tissues, with the highest levels in the TNBC subtype. When LHPP was knocked out in the MDA-MB-231 human TNBC cell line, cell proliferation, wound healing capacity, and invasion were significantly reduced. However, LHPP knockout in TNBC cells did not affect the phosphohistidine protein levels. Interestingly, LHPP knockout in MDA-MB-231 cells delayed tumor growth and reduced metastasis when orthotopically transplanted into mouse mammary glands. To investigate LHPP's role in breast cancer progression, we used next-generation sequencing and proximity-labeling proteomics, and found that LHPP regulates gene expression in chemokine-mediated signaling and actin cytoskeleton organization. Depletion of LHPP reduced the presence of tumor-infiltrating macrophages in mouse xenografts. Our results uncover a new tumor promoter role for LHPP phosphohistidine phosphatase in TNBC and suggest that targeting LHPP phosphatase could be a potential therapeutic strategy for TNBC.

Value of quantitative microsurface structure analysis for evaluating the invasion depth of type 0-II early gastric cancer.

Background and Aim: The microsurface structure reflects the degree of damage to the glands, which is related to the invasion depth of early gastric cancer. To evaluate the diagnostic value of quantitative microsurface structure analysis for estimating the invasion depth of early gastric cancer. Methods: White-light imaging and narrow-band imaging (NBI) endoscopy were used to visualize the lesions of the included patients. The area ratio and depth-predicting score (DPS) of each patient were calculated; meanwhile, each lesion was examined by endoscopic ultrasonography (EUS). Results: Ninety-three patients were included between 2016 and 2019. Microsurface structure is related to the histological differentiation and progression of early gastric cancer. The receiver operating characteristic curve showed that when an area ratio of 80.3% was used as a cut-off value for distinguishing mucosal (M) and submucosal (SM) type 0-II gastric cancers, the sensitivity, specificity, and accuracy were 82.9%, 80.2%, and 91.6%, respectively. The accuracies for distinguishing M/SM differentiated and undifferentiated early gastric cancers were 87.4% and 84.8%, respectively. The accuracy of EUS for distinguishing M/SM early gastric cancer was 74.9%. DPS can only distinguish M-SM1 (SM infiltration <500 µm)/SM (SM infiltration ≥500 µm) with an accuracy of 83.8%. The accuracy of using area ratio for distinguishing 0-II early gastric cancers was better than those of using DPS and EUS (P < 0.05). Conclusion: Quantitative analysis of microsurface structure can be performed to assess M/SM type 0-II gastric cancer and is expected to be effective for judging the invasion depth of gastric cancer.

Oxidative stress response: a critical factor affecting the ecological competitiveness of Streptococcus mutans.

Oral microecological balance is closely associated with the development of dental caries. Oxidative stress is one of the important factors regulating the composition and structure of the oral microbial community. Streptococcus mutans is linked to the occurrence and development of dental caries. The ability of S. mutans to withstand oxidative stress affects its survival competitiveness in biofilms. The oxidative stress regulatory mechanisms of S. mutans include synthesis of reductase, regulation of metal ions uptake, regulator PerR, transcription regulator Spx, extracellular uptake of glutathione, and other related signal transduction systems. Here, we provide an overview of how S. mutans adapts to oxidative stress and its influence on oral microecology, which may offer novel options to investigate the cariogenic mechanisms of S. mutans in the oral microenvironment, and new targets for the ecological prevention and treatment of dental caries.

A Comprehensive Review of Surface Acoustic Wave-Enabled Acoustic Droplet Ejection Technology and Its Applications.

This review focuses on the development of surface acoustic wave-enabled acoustic drop ejection (SAW-ADE) technology, which utilizes surface acoustic waves to eject droplets from liquids without touching the sample. The technology offers advantages such as high throughput, high precision, non-contact, and integration with automated systems while saving samples and reagents. The article first provides an overview of the SAW-ADE technology, including its basic theory, simulation verification, and comparison with other types of acoustic drop ejection technology. The influencing factors of SAW-ADE technology are classified into four categories: fluid properties, device configuration, presence of channels or chambers, and driving signals. The influencing factors discussed in detail from various aspects, such as the volume, viscosity, and surface tension of the liquid; the type of substrate material, interdigital transducers, and the driving waveform; sessile droplets and fluid in channels/chambers; and the power, frequency, and modulation of the input signal. The ejection performance of droplets is influenced by various factors, and their optimization can be achieved by taking into account all of the above factors and designing appropriate configurations. Additionally, the article briefly introduces the application scenarios of SAW-ADE technology in bioprinters and chemical analyses and provides prospects for future development. The article contributes to the field of microfluidics and lab-on-a-chip technology and may help researchers to design and optimize SAW-ADE systems for specific applications.

Down-regulation of histone deacetylase 7 reduces biological activities of retinal microvascular endothelial cells under high glucose condition and related mechanism.

AIM: To investigate the expression and effect of histone deacetylase 7 (HDAC7) in human retinal microvascular endothelial cells (HRMECs) under high glucose condition and related mechanism, and the expression of HDAC7 in the retinal tissue in diabetic rats. METHODS: The expression of HDAC7 in HRMECs under high glucose and the retinal tissue from normal or diabetic rats were detected with immunohistochemistry and Western blot. LV-shHDAC7 HRMECs were used to study the effect of HDAC7 on cell activities. Cell count kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, scratch test, Transwell test and tube formation assay were used to examine the ability of cell proliferation, migration, and angiogenesis. Finally, a preliminary exploration of its mechanism was performed by Western blot. RESULTS: The expression of HDAC7 was both up-regulated in retinal tissues of diabetic rats and high glucose-treated HRMECs. Down-regulation of HDAC7 expression significantly reduced the ability of proliferation, migration, and tube formation, and reversed the high glucose-induced high expression of CDK1/Cyclin B1 and vascular endothelial growth factor in high glucose-treated HRMECs. CONCLUSION: High glucose can up-regulate the expression of HDAC7 in HRMECs. Down-regulation of HDAC7 can inhibit HRMECs activities. HDAC7 is proposed to be involved in pathogenesis of diabetic retinopathy and a therapeutic target.

Building a Human Physiologically Based Pharmacokinetic Model for Aflatoxin B1 to Simulate Interactions with Drugs.

Mycotoxins such as aflatoxin B1 (AFB1) are secondary fungal metabolites present in food commodities and part of one's daily exposure, especially in certain regions, e.g., sub-Saharan Africa. AFB1 is mostly metabolised by cytochrome P450 (CYP) enzymes, namely, CYP1A2 and CYP3A4. As a consequence of chronic exposure, it is interesting to check for interactions with drugs taken concomitantly. A physiologically based pharmacokinetic (PBPK) model was developed based on the literature and in-house-generated in vitro data to characterise the pharmacokinetics (PK) of AFB1. The substrate file was used in different populations (Chinese, North European Caucasian and Black South African), provided by SimCYP® software (v21), to evaluate the impact of populations on AFB1 PK. The model's performance was verified against published human in vivo PK parameters, with AUC ratios and Cmax ratios being within the 0.5-2.0-fold range. Effects on AFB1 PK were observed with commonly prescribed drugs in South Africa, leading to clearance ratios of 0.54 to 4.13. The simulations revealed that CYP3A4/CYP1A2 inducer/inhibitor drugs might have an impact on AFB1 metabolism, altering exposure to carcinogenic metabolites. AFB1 did not have effects on the PK of drugs at representative exposure concentrations. Therefore, chronic AFB1 exposure is unlikely to impact the PK of drugs taken concomitantly.

[Effects of electroacupuncture pretreatment on NLRP3 inflammasome in mice with ventilator-induced lung injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment on inflammatory response in ven-tilator-induced lung injury (VILI) mice, so as to explore the underlying mechanism of EA pretreatment on prevention of VILI. METHODS: C57BL/6 mice were randomly divided into sham-operation group, model group, EA group and sham-acupoint group，with 8 mice in each group. The VILI model was established by ventilation with high tidal volume. Mice in the EA group and sham-acupoint group were given EA at "Zusanli" (ST36)and "Feishu"(BL13) or non-acupoints (located at 1-2 cm on both sides of the tail root of the proximal trunk) before mechanical ventilation, 30 min each time, once a day for 5 days. Arterial blood was collec-ted for blood gas analysis, the total protein content in bronchoalveolar lavage fluid (BALF) was detected by BCA method. The contents of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in BALF were detected by ELISA. Lung injury score was determined after HE staining. The protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and Caspase-1 in lung tissue was detected by Western blot. RESULTS: Compared with the sham-operation group, the arterial partial pressure of oxygen and oxygenation index were decreased(P<0.05), the levels of total protein, IL-1ß and IL-18 in BALF, the W/D value and the pathological injury score of lung tissue and the protein expression levels of NLRP3, Caspase-1 and ASC were increased(P<0.05)in the model group. Following the interventions, the above mentioned increased or decreased indicators were reversed(P<0.05) in the EA group rather than in the sham-acupoint group. CONCLUSION: EA pretreatment of ST36 and BL13 can reduce the damage of lung tissue caused by mechanical ventilation, which may be related to its effect in reducing the expression of NLPR3 inflammasome related proteins, reducing the activation of inflammasome, and thereby reducing the inflammatory response.

Optimization Analysis of Particle Separation Parameters for a Standing Surface Acoustic Wave Acoustofluidic Chip.

Microparticle separation technology is an important technology in many biomedical and chemical engineering applications from sample detection to disease diagnosis. Although a variety of microparticle separation techniques have been developed thus far, surface acoustic wave (SAW)-based microfluidic separation technology shows great potential because of its high throughput, high precision, and integration with polydimethylsiloxane (PDMS) microchannels. In this work, we demonstrate an acoustofluidic separation chip that includes a piezoelectric device that generates tilted-angle standing SAWs and a permanently bonded PDMS microchannel. We established a mathematical model of particle motion in the microchannel, simulated the particle trajectory through finite element simulation and numerical simulation, and then verified the validity of the model through acoustophoresis experiments. To improve the performance of the separation chip, the influences of particle size, flow rate, and input power on the particle deflection distance were studied. These parameters are closely related to the separation purity and separation efficiency. By optimizing the control parameters, the separation of micron and submicron particles under different throughput conditions was achieved. Moreover, the separation samples were quantitatively analyzed by digital light scattering technology and flow cytometry, and the results showed that the maximum purity of the separated particles was ∼95%, while the maximum efficiency was ∼97%.

[Characteristics of Soil Erosion and Nitrogen Loss in Vegetable Field Under Natural Rainfall].

The effects of vegetable planting on soil loss and nutrient loss, runoff, soil erosion, and nitrogen (ammonium nitrogen and nitrate nitrogen) losses under individual rainfalls of fruit- and leaf-vegetable fields between April to October in 2021 were observed using in-situ observation testing. The results showed that: ① the runoff, erosion, and nitrogen loss of the fruit-vegetable pattern (eggplant-chili) were 1.27-2.00 times those under the leaf-vegetable pattern (leaf lettuce-sweet potato leaves), especially under the second season vegetable period. Those losses under the second season vegetable accounted for 50.86%-68.83% of the total losses under different vegetable patterns, which were approximately 1.03-2.04 times those under the first season vegetable. The runoff, erosion, and nutrient loss of vegetable fields under different treatments were both concentrated in June and July, and the nitrogen loss was mainly in the form of nitrate nitrogen with surface runoff. ② The runoff, erosion, and nutrient losses under individual rainfalls of vegetable fields under different treatments fluctuated among the vegetable growing season, and the losses were mainly concentrated in several typical rainfall events. On the whole, the loss and concentration of nitrate and ammonium nitrogen in runoff and erosion sediment of vegetables in the first season were lower than those in the second season. The runoff, erosion, and loss of ammonium nitrogen and nitrate nitrogen of fruit-vegetable were higher than those of leaf-vegetable. ③ Both rainfall amount and maximum 30 min rainfall intensity had significantly positive effects on runoff, soil loss, and nitrogen loss. Runoff, erosion, and nutrient losses under different vegetable patterns were mainly generated by moderate rain, heavy rain, and heavy rainstorms, which accounted for 29.58%-46.68%, 24.54%-36.79%, and 24.01%-39.13% of the total losses, respectively. The results also showed that soil erosion and nutrient losses generated by different rainfall grades were obviously different for the fruit- and leaf-vegetable treatments. The results indicated that the vegetable pattern had significant impacts on soil loss and nutrient loss, and the leaf-vegetable pattern could reduce soil erosion and nutrient loss compared with the fruit-vegetable pattern. Furthermore, for different vegetable patterns and vegetable growing seasons, the effects of rainfall on soil loss and nutrient loss were quite different. The results of this study were helpful in clarifying the soil erosion and nutrient loss characteristics of vegetable fields in South China.

The role of bacterial cyclic di-adenosine monophosphate in the host immune response.

Cyclic di-adenosine monophosphate (c-di-AMP) is a second messenger which is widely used in signal transduction in bacteria and archaea. c-di-AMP plays an important role in the regulation of bacterial physiological activities, such as the cell cycle, cell wall stability, environmental stress response, and biofilm formation. Moreover, c-di-AMP produced by pathogens can be recognized by host cells for the activation of innate immune responses. It can induce type I interferon (IFN) response in a stimulator of interferon genes (STING)-dependent manner, activate the nuclear factor kappa B (NF-κB) pathway, inflammasome, and host autophagy, and promote the production and secretion of cytokines. In addition, c-di-AMP is capable of triggering a host mucosal immune response as a mucosal adjuvant. Therefore, c-di-AMP is now considered to be a new pathogen-associated molecular pattern in host immunity and has become a promising target in bacterial/viral vaccine and drug research. In this review, we discussed the crosstalk between bacteria and host immunity mediated by c-di-AMP and addressed the role of c-di-AMP as a mucosal adjuvant in boosting evoked immune responses of subunit vaccines. The potential application of c-di-AMP in immunomodulation and immunotherapy was also discussed in this review.

The Effect of Electroacupuncture Preconditioning on Regional Cerebral Oxygen Saturation Levels in Elderly Patients with Diabetes.

Objective: This study aimed to evaluate the effect of electroacupuncture preconditioning on regional cerebral oxygen saturation (rSO2) levels in elderly patients with diabetes. Methods: Forty patients undergoing elective diabetic foot surgery were enrolled in this study. All patients were aged 65 years and above and weighed 45-75 kg. All were characterized as class II or III according to the American Society of Anesthesiologists' physical status classification system. Patients were divided randomly into an electroacupuncture group (group E) and a control group (group C); both groups comprised 20 patients. In group E, the DU20 (Baihui), DU24 (Shenting), and EX-HN1 (Sishencong) acupoints were selected for electroacupuncture 30 min prior to administering anesthesia, while in group C, patients underwent routine anesthesia without electroacupuncture. The patients in both groups were anesthetized using a sciatic nerve block. The number of cases with increased or decreased regional oxygen saturation (rSO2) compared with the baseline as well as rSO2 variability in the two groups were recorded and compared. Results: There was no significant difference in the preoperative rSO2 values between the two groups (54.4 ± 4.8 (L), 53.9 ± 5.2 (R) [group C] vs 54.1 ± 5.2 (L), 54.5 ± 4.6 (R)[group E]). Compared with group C, the rSO2 in group E increased (50.3 ± 3.9 [group C] vs 58.4 ± 3.2[group E]), and this difference was statistically significant (P < 0.001). Conclusion: Electroacupuncture stimulation can increase rSO2 levels in patients with diabetes. Clinical Registration Number: ChiCTR2100048783 (http://www.chictr.org.cn).

The Role of Mitochondrial Quality Control in Cognitive Dysfunction in Diabetes.

Type 2 diabetes (T2DM) is a well known risk factor for Alzheimer's disease. Mitochondria are the center of intracellular energy metabolism and the main source of reactive oxygen species. Mitochondrial dysfunction has been identified as a key factor in diabetes-associated brain alterations contributing to neurodegenerative events. Defective insulin signaling may act in concert with neurodegenerative mechanisms leading to abnormalities in mitochondrial structure and function. Mitochondrial dysfunction triggers neuronal energy exhaustion and oxidative stress, leading to brain neuronal damage and cognitive impairment. The normality of mitochondrial function is basically maintained by mitochondrial quality control mechanisms. In T2DM, defects in the mitochondrial quality control pathway in the brain have been found to lead to mitochondrial dysfunction and cognitive impairment. Here, we discuss the association of mitochondrial dysfunction with T2DM and cognitive impairment. We also review the molecular mechanisms of mitochondrial quality control and impacts of mitochondrial quality control on the progression of cognitive impairment in T2DM.

Experimental research on surface acoustic wave microfluidic atomization for drug delivery.

This paper demonstrates that surface acoustic wave (SAW) atomization can produce suitable aerosol concentration and size distribution for efficient inhaled lung drug delivery and is a potential atomization device for asthma treatment. Using the SAW device, we present comprehensive experimental results exploring the complexity of the acoustic atomization process and the influence of input power, device frequency, and liquid flow rate on aerosol size distribution. It is hoped that these studies will explain the mechanism of SAW atomization aerosol generation and how they can be controlled. The insights from the high-speed flow visualization studies reveal that it is possible by setting the input power above 4.17 W, thus allowing atomization to occur from a relatively thin film, forming dense, monodisperse aerosols. Moreover, we found that the aerosol droplet size can be effectively changed by adjusting the input power and liquid flow rate to change the film conditions. In this work, we proposed a method to realize drug atomization by a microfluidic channel. A SU-8 flow channel was prepared on the surface of a piezoelectric substrate by photolithography technology. Combined with the silicon dioxide coating process and PDMS process closed microfluidic channel was prepared, and continuous drug atomization was provided to improve the deposition efficiency of drug atomization by microfluidic.