Single-cell RNA sequencing analysis to evaluate antimony exposure effects on cell-lineage communications within the Drosophila testicular niche.

The increasing production and prevalence of antimony (Sb)-related products raise concerns regarding its potential hazards to reproductive health. Upon environmental exposure, Sb reportedly induces testicular toxicity during spermatogenesis; moreover, it is known to affect various testicular cell populations, particularly germline stem cell populations. However, the cell-cell communication resulting from Sb exposure within the testicular niche remains poorly understood. To address this gap, herein we analyzed testicular single-cell RNA sequencing data from Sb-exposed Drosophila. Our findings revealed that the epidermal growth factor receptor (EGFR) and WNT signaling pathways were associated with the stem cell niche in Drosophila testes, which may disrupt the homeostasis of the testicular niche in Drosophila. Furthermore, we identified several ligand-receptor pairs, facilitating the elucidation of intercellular crosstalk involved in Sb-mediated reproductive toxicology. We employed scRNA-seq analysis and conducted functional verification to investigate the expression patterns of core downstream factors associated with EGFR and WNT signatures in the testes under the influence of Sb exposure. Altogether, our results shed light on the potential mechanisms of Sb exposure-mediated testicular cell-lineage communications.

Weak-value amplified surface plasmon resonance sensor based on joint detection of optical activity and refractive index.

A versatile system combining surface plasmon resonance (SPR) and weak value amplification (WVA) is presented, which can measure the optical activity and refractive index of chiral/achiral molecules, ionic compounds, and their mixture in solution individually or simultaneously. The variations in output light intensity directly exhibit high sensitivity to changes in optical activity and refractive index of the aforementioned substances. Furthermore, by examining the correlation between the intensity variation trend and the optical activity of the chiral molecule, the molecule's absolute configuration can be ascertained. Utilizing this instrument, optical rotation with a resolution of 3.04 × 10-6 rad and refractive index with a resolution of 5.57 × 10-9 RIU were obtained. As an attempt at practical application, this sensor was used to detect the adulteration of glucose and fructose in pure honey. Not only can such compromised honey be distinguished from pure honey using the refractive index or optical rotation, but the difference in optical activity can also be employed to effectively differentiate between adulterated honey samples containing glucose and fructose separately.

Intelligent water perimeter security event recognition based on NAM-MAE and distributed optic fiber acoustic sensing system.

Distributed optical acoustic sensing (DAS) based on phase-sensitive optical time-domain reflectometry can realize the distributed monitoring of multi-point disturbances along an optical fiber, thus making it suitable for water perimeter security applications. However, owing to the complex environment and the production of various noises by the system, continuous and effective recognition of disturbance signals becomes difficult. In this study, we propose a Noise Adaptive Mask-Masked Autoencoders (NAM-MAE) algorithm based on the novel mask mode of a Masked Autoencoders (MAE) and applies it to the intelligent event recognition in DAS. In this method, fewer but more accurate features are fed into the deep learning model for recognition by directly shielding the noise. Taking the fading noise generated by the system as an example, data on water perimeter security events collected in DAS underwater acoustic experiments are used. The NAM-MAE is compared with other models. The results indicate higher training accuracy and higher convergence speed of NAM-MAE than other models. Further, the final test accuracy reaches 96.6134%. It can be demonstrated that the proposed method has feasibility and superiority.

Organelle Imaging with Terahertz Scattering-Type Scanning Near-Field Microscope.

Organelles play core roles in living beings, especially in internal cellular actions, but the hidden information inside the cell is difficult to extract in a label-free manner. In recent years, terahertz (THz) imaging has attracted much attention because of its penetration depth in nonpolar and non-metallic materials and label-free, non-invasive and non-ionizing ability to obtain the interior information of bio-samples. However, the low spatial resolution of traditional far-field THz imaging systems and the weak dielectric contrast of biological samples hinder the application of this technology in the biological field. In this paper, we used an advanced THz scattering near-field imaging method for detecting chloroplasts on gold substrate with nano-flatness combined with an image processing method to remove the background noise and successfully obtained the subcellular-grade internal reticular structure from an Arabidopsis chloroplast THz image. In contrast, little inner information could be observed in the tea chloroplast in similar THz images. Further, transmission electron microscopy (TEM) and mass spectroscopy (MS) were also used to detect structural and chemical differences inside the chloroplasts of Arabidopsis and tea plants. The preliminary results suggested that the interspecific different THz information is related to the internal spatial structures of chloroplasts and metabolite differences among species. Therefore, this method could open a new way to study the structure of individual organelles.

Genetic and In Vitro Characteristics of a Porcine Circovirus Type 3 Isolate from Northeast China.

Porcine circovirus 3 (PCV3) is an emerging virus first discovered in the United States in 2015, and since then, PCV3 has been found in many regions of the world, including America, Asia, and Europe. Although several PCV3 investigations have been carried out, there is a lack of knowledge regarding the pathogenicity of PCV3, mostly due to the limited number of PCV3 isolates that are readily available. In this study, PCV3-DB-1 was isolated in PK-15 cells and characterized in vitro. Electron microscopy revealed the presence of PCV-like particles, and in situ hybridization RNA analysis demonstrated the replication of PCV3 in PK-15 cell culture. Based on phylogenetic analysis of PCV3 isolates from the Heilongjiang province of China, PCV3-DB-1 with 24 alanine and 27 lysine in the Cap protein was originally isolated and determined to belong to the clade PCV3a.

Yinchenhao Tang alleviates high fat diet induced NAFLD by increasing NR1H4 and APOA1 expression.

Background and aim: Traditional Chinese medicine Yinchenhao Tang (YCHT) demonstrated benefits when treating nonalcoholic fatty liver disease (NAFLD), but the dose effects and potential targets are still ambiguous. In this study, different concentrations of YCHT were employed to treat NAFLD and the underlying therapeutic targets were investigated. Experimental procedure: Kunming mice were fed with high fat diet (HFD) for 8 weeks to induce NAFLD, then treated with 3 different concentrations of YCHT. Hepatic pathological changes and serum lipid levels were examined. Network pharmacology was applied to screen the potential targets of YCHT for NAFLD modulation. NR1H4 and APOA1 expression was evaluated by QPCR and western blotting. Immunohistochemistry (IHC) staining was conducted to visualize the localization pattern of NR1H4 and APOA1 in the liver. Results: YCHT significantly reduced liver lipid storage and improved the liver pathological status of NAFLD mice. The serum lipid levels, as well as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, were remarkably reduced by the middle and high dose YCHT. There are 35 potential targets for YCHT to regulate NAFLD. HFD suppressed both RNA and protein expression of NR1H4 and APOA1, while YCHT elevated NR1H4 and APOA1 expression. IHC staining indicated that NR1H4 was mainly located in the cell nucleus and the APOA1 signal was observed at the liver sinusoid or cytoplasm. Conclusion: YCHT can effectively ameliorate HFD induced NAFLD by modulating the promising targets of NR1H4 and APOA1.

Label-free detection and identification of single bacteria via terahertz near-field imaging.

In recent years, terahertz (THz) imaging has attracted much attention because of its ability to obtain physical and chemical information in a label-free, noninvasive and nonionizing manner. However, the low spatial resolution of traditional THz imaging systems and the weak dielectric response of biological samples hinder the application of this technology in the biomedical field. In this paper, we report a new THz near-field imaging method for a single bacteria, through the coupling effect of nanoscale radius of probe and platinum gold substrate, which greatly enhances THz near-field signal of biological samples. A THz super-resolution image of bacteria has been successfully obtained by strictly controlling the relevant test parameters such as tip parameters and driving amplitude. By analyzing and processing the THz spectral image, the morphology and inner structure of bacteria have been observed. The method has been used to detect and identify Escherichia coli represented by Gram-negative bacteria and Staphylococcus aureus represented by Gram-positive bacteria. This application provides a new label-free, noninvasive and nonionizing testing protocol for the detection of single bacteria.

AIEgens/Mitochondria Nanohybrids as Bioactive Microwave Sensitizers for Non-Thermal Microwave Cancer Therapy.

Aggregation-induced emission luminogens (AIEgens) are widely used as photosensitizers for image-guided photodynamic therapy (PDT). Due to the limited penetration depth of light in biological tissues, the treatments of deep-seated tumors by visible-light-sensitized aggregation-induced emission (AIE) photosensitizers are severely hampered. Microwave dynamic therapy attracts much attention because microwave irradiation can penetrate very deep tissues and sensitize the photosensitizers to generate reactive oxygen species (ROS). In this work, a mitochondrial-targeting AIEgen (DCPy) is integrated with living mitochondria to form a bioactive AIE nanohybrid. This nanohybrid can not only generate ROS under microwave irradiation to induce apoptosis of deep-seated cancer cells but also reprogram the metabolism pathway of cancer cells through retrieving oxidative phosphorylation (OXPHOS) instead of glycolysis to enhance the efficiency of microwave dynamic therapy. This work demonstrates an effective strategy to integrate synthetic AIEgens and natural living organelles, which would inspire more researchers to develop advanced bioactive nanohybrids for cancer synergistic therapy.

Terahertz spectroscopic monitoring and analysis of citrus leaf water status under low temperature stress.

Low temperature stress, in the form of chilling and freezing, is one of the major environmental factors impacting on citrus yield, which changes plant's water state and results in the crops' sub-health or injury. The innovative terahertz (THz) spectroscopy and imaging based sensing technology has been shown to be a suitable tool for plant leaf water status determination, due to THz radiation's innate sensitivity to hydrogen bond vibration in aqueous solutions, which is usually related to plant phenotype change. We demonstrate experimentally that the THz absorption coefficient of leaf could be used for distinguishing plant's physiological stress status, exhibiting clear decreasing or increasing trend under chilling or freezing stress respectively. The underlying rationale might be that membrane damage shows a diverse pattern, changing the intra- or extra-cellular liquid environments, likely being linked to the various THz spectral characteristics. There were different adaptations in leaf morphology, leading to different leaf density, which in turn affects the water volume fraction. Moreover, different patterns of the dynamic equilibrium state of free water and bound water under chilling and freezing treatment were revealed by THz spectroscopy. Here, THz spectroscopic monitoring has shown unique potential for judging citrus's low temperature stress state through bio-water detection and discrimination.

Walk-through millimeter wave imaging testbed based on double multistatic cross arrays.

A walk-through millimeter wave imaging testbed using double multistatic cross arrays is presented. The imaging testbed consists of a vector network analyzer, a power amplifier, a low-noise amplifier, 36 SP6T electrical switchers, and double homemade multistatic cross arrays placed on both sides of the imaging area. The imaging algorithm based on the range migration algorithm is deduced, and the imaging performance is analyzed. The metallic ball experimental results show that the imaging resolution is close to the theoretical value, and demonstrate the imaging feasibility of the testbed working in mutual mode.

Metformin and Gegen Qinlian Decoction boost islet α-cell proliferation of the STZ induced diabetic rats.

BACKGROUND: The traditional Chinese medicine Gegen Qinlian Decoction (GQD), as well as metformin, had been reported with anti-diabetic effects in clinical practice. OBJECTIVE: To verify whether these two medicines effectively ameliorate hyperglycemia caused by deficiency of islet ß-cell mass which occurs in both type 1 and type 2 diabetes. METHODS: SD rats were injected with a single dose of STZ (55 mg/kg) to induce ß-cell destruction. The rats were then divided into control, diabetes, GQD and metformin group. GQD and metformin groups were administered with GQD extract or metformin for 6 weeks. The islet α-cell or ß-cell mass changes were tested by immunohistochemical and immunofluorescent staining. The potential targets and mechanisms of GQD and metformin on cell proliferation were tested using in silico network pharmacology. Real-time PCR was performed to test the expression of islet cells related genes and targets related genes. RESULTS: Both GQD and metformin did not significantly reduce the FBG level caused by ß-cell mass reduction, but alleviated liver and pancreas histopathology. Both GQD and metformin did not change the insulin positive cell mass but increased α-cell proliferation of the diabetic rats. Gene expression analysis showed that GQD and metformin significantly increased the targets gene cyclin-dependent kinase 4 (Cdk4) and insulin receptor substrate (Irs1) level. CONCLUSION: This research indicates that GQD and metformin significantly increased the α-cell proliferation of ß-cell deficiency induced diabetic rats by restoring Cdk4 and Irs1 gene expression.

Deep learning aided quantitative analysis of anti-tuberculosis fixed-dose combinatorial formulation by terahertz spectroscopy.

Anti-tuberculosis fixed-dose combinatorial formulation (FDCs) is an effective drug for the treatment of tuberculosis. As a compound medicine, its efficacy is based on the comprehensive action of multiple main ingredients. If the content of an active ingredient is insufficient, not only will it reduce the curative effect, but it also causes patients to develop drug resistance and leads to the evolution of drug-resistant strains of tuberculosis, which hamper the treatment of the disease. Thus accurate detection of the contents of active components in the anti-tuberculosis FDC is the key link of its quality control. For the first time, convolutional neural networks (CNN), one of the most popular deep learning methods, is adopted to develop a quantitative calibration model based on terahertz time-domain spectroscopy (THz-TDS) for the accurate detection of the content of each active component in the anti-tuberculosis FDCs. For comparison with CNN, partial least squares regression (PLSR) was also introduced to build a reference quantitative calibration model. For CNN modeling, the raw THz spectral is fed to the model directly; While for PLSR, prior to the spectrum feeding to the model, the raw spectral data are processed by multiple different combinations of preprocessing. Experimental and simulation results demonstrate that although preprocessing techniques can improve the prediction performance of PLSR, its prediction capabilities is still inferior to CNN based on raw spectrum. Therefore, for the quantitative analysis of the content of each active component in the anti-tuberculosis FDCs, CNN appears to be an ideal modeling method.

Aperture-type terahertz near-field imaging with a cylindrical frustum-shaped plastic probe.

We designed an aluminum-coated plastic probe made from the combination of cylinder and a frustum of a cone for terahertz near-field imaging. The bunching width of the probe is 12 µm and the electric field intensity enhancement factor just outside the probe tip reaches up to 25. An imaging resolution obtained through near-field imaging experiments on a variety of targets, including narrow metals and narrow media, is 6 µm (λ/450) at 0.11 THz. By adopting an adaptive threshold segmentation image processing algorithm that combines Hilbert scanning and wavelet transform, the influence of a large area of metal near the imaging area on the imaging result is successfully suppressed. Imaging of a scratch on the plastic substrate makes the new probe feasible for quality identification of nonmetallic cultural relics.

Pathogenic Characterization of a Porcine Circovirus Type 3 Isolate from Heilongjiang, China.

The clinical outcome of porcine circovirus 3 (PCV3) infection is still controversial. Herein, a novel PCV3 isolate (PCV3-China/DB-1/2017) with the molecular characterization of 24A and 27K in the Cap protein was used to inoculate three-week-old cesarean-derived, colostrum-deprived piglets. The nine PCV3 DB-1 inoculated piglets exhibited no obvious clinical symptoms or macroscopic lesions. PCV3 displayed a broad histotropism, including the heart, liver, spleen, lung, kidney, brain, lymph nodes, and tonsil, and the lungs and lymph nodes contained a higher quantity of viral genomes compared to that of the other organs. From 7 days after PCV3 DB-1 inoculation, the piglets showed obvious IgG antibody responses against PCV3 rCap-VLPs. The cumulative results demonstrated that PCV3 trend to low pathogenicity.

Low terahertz-band scanning near-field microscope with 155-nm resolution.

We report on the design and implementation of a scattering-type scanning near-field microscope working in the low terahertz-band under ambient conditions for nanoscopic investigations of physical properties and characteristics at sample surfaces and interfaces in the microwave and millimeter wave bands. Employing a nano-tip that oscillates vertically at a frequency Ω as the antenna, and a subharmonic mixer as the receiver, and corresponding demodulation algorithms, the back-scattered light carrying tip-sample interaction information is effectively extracted, while excluding almost all of the background noises. The amplitude and phase images constructed from signals demodulated at various harmonics (nΩ, n = 1 - 4) are obtained while scanning an Au-Si step structure with the newly developed microscope, and a resolution of 155 nm (~λ/20,000) has been demonstrated at the fourth harmonic frequency (4Ω) working at 110 GHz, with signal-to-noise ratio (SNR) equal to 44.4 dB on the Au surface and 36.2 dB on the Si surface, demonstrating the power of this new instrument for micro/nano-resolution studies in the millimeter wave band.

A solid-state nanopore-based single-molecule approach for label-free characterization of plant polysaccharides.

Polysaccharides are important biomacromolecules existing in all plants, most of which are integrated into a fibrillar structure called the cell wall. In the absence of an effective methodology for polysaccharide analysis that arises from compositional heterogeneity and structural flexibility, our knowledge of cell wall architecture and function is greatly constrained. Here, we develop a single-molecule approach for identifying plant polysaccharides with acetylated modification levels. We designed a solid-state nanopore sensor supported by a free-standing SiN x membrane in fluidic cells. This device was able to detect cell wall polysaccharide xylans at concentrations as low as 5 ng/µL and discriminate xylans with hyperacetylated and unacetylated modifications. We further demonstrated the capability of this method in distinguishing arabinoxylan and glucuronoxylan in monocot and dicot plants. Combining the data for categorizing polysaccharide mixtures, our study establishes a single-molecule platform for polysaccharide analysis, opening a new avenue for understanding cell wall structures, and expanding polysaccharide applications.

Poly(3-hydroxypropionate): Biosynthesis Pathways and Malonyl-CoA Biosensor Material Properties.

Many single-use non-degradable plastics are a threat to life today, and several polyhydroxyalkanoates (PHAs) biopolymers have been developed in the bioplastic industry to place petrochemical-based plastics. One of such is the novel biomaterial poly(3-hydroxypropionate) [poly(3HP)] because of its biocompatibility, biodegradability, and high yield synthesis using engineered strains. To date, many bio-polymer-based functional composites have been developed to increase the value of raw microbial-biopolymers obtained from cheap sources. This review article broadly covers poly(3HP), a comprehensive summary of critical biosynthetic production pathways comparing the yields and titers achieved in different Microbial cell Factories. This article also provides extensive knowledge and highlights recent progress on biosensors' use to optimize poly(3HP) production, some bacteria host adopted for production, chemical and physical properties, life cycle assessment for poly(3HP) production using corn oil as carbon source, and some essential medical applications of poly(3HP).

Detection of gene mutation responsible for Huntington's disease by terahertz attenuated total reflection microfluidic spectroscopy.

Terahertz absorption spectroscopy based on attenuated total reflection (ATR) from a microfluidic sample cell was designed and implemented to detect gene mutations leading to Huntington's disease (HD). The self-developed compact ATR microfluidic system was employed to detect two groups of base-repeated DNA molecules combined with a terahertz time-domain spectrometer in a marker-free manner. The first group featured different repetition patterns of oligonucleotide fragments, and the second group included the HD gene. For the oligonucleotides of different repetition patterns, there were significant differences among the three oligonucleotides with three repeats of the double bases, which could be unambiguously classified and identified; For the HD gene, it was found that the magnitude of the terahertz absorption coefficients of the four oligonucleotide solutions was, in ascending order, CAG-4 < CAG-16 < CAG-32 < CAG-40 (the numbers are the repeat times of the CAG base segment, with 40 repeats belonging to the HD gene), when the concentration of oligonucleotide was 1 mg/mL. Principal component analysis result indicated that the spectral differences of the four oligonucleotide solutions with different CAG repeat times were statistically significant and clearly distinguishable. These results demonstrate the potential of terahertz spectroscopy as a noninvasive, unmarked, fast and low-cost assay for gene diagnosis and clinical disease detection.

Impaired frontal-parietal control network in chronic prostatitis/chronic pelvic pain syndrome revealed by graph theoretical analysis: A DTI study.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by chronic pain in pelvic area and lower urinary tract symptoms (LUTS). Previous neuroimaging studies demonstrated that chronic pain was associated with the altered brain activity. However, the pathological mechanisms associated with altered brain control of CP/CPPS are not well-understood. Therefore, we sought to investigate the topological properties of white matter brain networks in patients with CP/CPPS and whether the topological configuration of frontal-parietal control network was disrupted. We collected 19 patients with CP/CPPS and 32 matched healthy controls (HCs). Diffusion tensor imaging data of all participates were used to map the white matter structural networks. Graph theoretical method was applied to investigate the alterations of topological properties of brain network in patients. Moreover, we also investigated whether the alerted brain regions might be correlated with any clinical features of patients by the method of Pearson correlation analysis. Both CP/CPPS patients and HCs exhibited a 'small-world' behavior or economical small-world architecture of the white matter brain networks. In addition, CP/CPPS had a lower global efficiency in the right middle frontal gyrus (orbital part) and a higher global efficiency in the left middle cingulate and paracingulate gyri. CP/CPPS also showed increased local efficiency in the left middle cingulate and paracingulate gyri and paracentral lobule. Moreover, the local efficiency of the left middle cingulate gyrus was positively correlated with the scores of the influence of symptoms on the quality of life. The local efficiency of the left precuneus and right supplementary motor area were positively correlated with the total scores of NIH-CPSI and the scores of pain and discomfort symptoms, respectively. Together, we found that patients with CP/CPPS had alterations of connections within the frontal-parietal control network, which suggested that the altered connectivity involved in the executive control processing procedures might contribute to the pathogenesis of the pelvic pain and LUTS in CP/CPPS. Thus these results provided new insights into the understanding of CP/CPPS.

Near-Field Nanoscopic Terahertz Imaging of Single Proteins.

Terahertz (THz) biological imaging has attracted intense attention due to its capability of acquiring physicochemical information in a label-free, noninvasive, and nonionizing manner. However, extending THz imaging to the single-molecule level remains a challenge, partly due to the weak THz reflectivity of biomolecules with low dielectric constants. Here, the development of graphene-mediated THz scattering-type scanning near-field optical microscope for direct imaging of single proteins is reported. Importantly, it is found that a graphene substrate with high THz reflectivity and atomic flatness can provide high THz contrast against the protein molecules. In addition, a platinum probe with an optimized shaft length is found enabling the enhancement of the amplitude of the scattered THz near-field signals. By coupling these effects, the topographical and THz scattering images of individual immunoglobulin G (IgG) and ferritin molecules with the size of a few nanometers are obtained, simultaneously. The demonstrated strategy thus opens new routes to imaging single biomolecules with THz.