On the imaging depth limit of photoacoustic tomography in the visible and first near-infrared windows.

It is well known that photoacoustic tomography (PAT) can circumvent the photon scattering problem in optical imaging and achieve high-contrast and high-resolution imaging at centimeter depths. However, after two decades of development, the long-standing question of the imaging depth limit of PAT in biological tissues remains unclear. Here we propose a numerical framework for evaluating the imaging depth limit of PAT in the visible and the first near-infrared windows. The established framework simulates the physical process of PAT and consists of seven modules, including tissue modelling, photon transportation, photon to ultrasound conversion, sound field propagation, signal reception, image reconstruction, and imaging depth evaluation. The framework can simulate the imaging depth limits in general tissues, such as the human breast, the human abdomen-liver tissues, and the rodent whole body and provide accurate evaluation results. The study elucidates the fundamental imaging depth limit of PAT in biological tissues and can provide useful guidance for practical experiments.

Enolase, a cadmium resistance related protein from hyperaccumulator plant Phytolacca americana, increase the tolerance of Escherichia coli to cadmium stress.

Phytolacca americana is a Cd hyperaccumulator plant that accumulates significant amounts of Cd in leaves, making it a valuable phytoremediation plant species. Our previous research found enolase (ENO) may play an important part in P. americana to cope with Cd stress. As a multifunctional enzyme, ENO was involved not only in glycolysis but also in the response of plants to various environmental stresses. However, there are few studies on the function of PaENO (P. americana enolase) in coping with Cd stress. In this study, the PaENO gene was isolated from P. americana, and the expression level of PaENO gene significantly increased after Cd treatment. The enzymatic activity analysis showed PaENO had typical ENO activity, and the 42-position serine was essential to the enzymatic activity of PaENO. The Cd resistance assay indicated the expression of PaENO remarkably enhanced the resistance of E. coli to Cd, which was achieved by reducing the Cd content in E. coli. Moreover, both the expression of inactive PaENO and PaMBP-1 (alternative translation product of PaENO) can improve the tolerance of E. coli to Cd. The results indicated PaENO may be alternatively translated into the transcription factor PaMBP-1 to participate in the response of P. americana to Cd stress.

The expression of the Cd resistance related protein PaENO can significantly increase the tolerance of E. coli to Cd, which was achieved by reducing the content of Cd in E. coli cells, and was independent of the enzymatic activity of PaENO. Moreover, PaENO may be alternatively translated into the transcription factor PaMBP-1 to participate in the response of P. americana to Cd stress.

Acceleration of Protein Degradation by 20S Proteasome-Binding Peptides Generated by In Vitro Artificial Evolution.

Although the 20S core particle (CP) of the proteasome is an important component of the 26S holoenzyme, the stand-alone 20S CP acts directly on intrinsically disordered and oxidized/damaged proteins to degrade them in a ubiquitin-independent manner. It has been postulated that some structural features of substrate proteins are recognized by the 20S CP to promote substrate uptake, but the mechanism of substrate recognition has not been fully elucidated. In this study, we screened peptides that bind to the 20S CP from a random eight-residue pool of amino acid sequences using complementary DNA display an in vitro molecular evolution technique. The identified 20S CP-binding amino acid sequence was chemically synthesized and its effects on the 20S CP were investigated. The 20S CP-binding peptide stimulated the proteolytic activity of the inactive form of 20S CP. The peptide bound directly to one of the α-subunits, opening a gate for substrate entry on the α-ring. Furthermore, the attachment of this peptide sequence to α-synuclein enhanced its degradation by the 20S CP in vitro. In addition to these results, docking simulations indicated that this peptide binds to the top surface of the α-ring. These peptides could function as a key to control the opening of the α-ring gate.

Small-core hollow-core nested antiresonant nodeless fiber with semi-circular tubes.

Hollow-core nested anti-resonant nodeless fibers (HC-NANFs) exhibit great performance in low loss and large bandwidth. Large core sizes are usually used to reduce confinement losses, but meanwhile, bring side effects such as high bending and coupling losses. This study proposes a small-core HC-NANF with a relatively low confinement loss. Semi-circular tubes (SCTs) are added to constitute the core boundary and reduce the fiber-core radius (R). Double NANFs tubes and single-ring tubes are added inside the SCTs to reduce loss. Simulation results show that the optimized structure with R of 5 µm has confinement loss and total loss of 0.687 dB/km and 4.27 dB/km at 1.55 µm, respectively. The bending loss is less than 10 dB/km at 1.4 ∼ 1.6 µm with a bending radius of 10 mm. The direct coupling loss with standard single mode fiber is greatly reduced to ∼ 0.125 dB compared to other HC-NANFs. The modified structure of HC-NANFs also shows a large bandwidth, effective single-mode operation, potentially high birefringence performance, and remarkable robustness of the optimized structure parameters, making it suitable for short-haul applications in laser-based gas sensing, miniaturized fiber sensing, etc.

Hybrid photonic bandgap effect in twisted hollow-core photonic bandgap fibers.

A hybrid photonic bandgap effect in twisted hollow-core photonic bandgap fibers (HC-PBFs) is theoretically investigated for the first time, to the best of our knowledge. Due to the topological effect, twisting of the fibers changes the effective refractive index and lifts the degeneracy of the photonic bandgap ranges of the cladding layers. This twist-induced hybrid photonic bandgap effect shifts up the center wavelength and narrows the bandwidth of the transmission spectrum. A quasi-single-mode low-loss transmission is achieved in the twisted 7-cell HC-PBFs with a twisting rate α = 7-8 rad/mm, which has a loss < 30 dB/km and higher-order mode extinction ratio > 15 dB. The twisted HC-PBFs could be suitable for applications such as spectral and mode filters.

Prognostic factors and related complications/sequalae of squamous cell carcinoma located in the gingivobuccal complex.

BACKGROUND: Gingivobuccal complex (GBC) was a relatively new concept of oral subsite that was comprises of the upper and/or lower gingiva, gingival buccal sulcus, and adjacent buccal mucosa. Squamous cell carcinoma (SCC) of the GBC had a poor prognosis, with few studies analyzing this particular entity. The objective of this study was to analyze the risk factors affecting the prognosis and complications/sequalae of gingivobuccal complex cancer. METHODS: Between December 2014 and August 2019, a total of 122 patients diagnosed with primary gingivobuccal complex cancer in Beijing Stomatological Hospital, Capital Medical University were enrolled in the study. Through outpatient reviewed and telephone followed-up for 2-5 years postoperatively, postoperative relapse and complications/sequalae were assessed. The primary outcome parameter was 2-year disease-free survival. RESULTS: The most common central site of the tumor was the buccal mucosa (45.1%), followed by the lower gingiva (36.9%). The most diseases were pT4a (45.1%) and there was lymph node invasion (pN+) in 41.8% of patients. Moderate differentiated squamous carcinoma (77.9%) accounted for the vast majority of the histopathological differentiation. A total of 62.3% of tumors invaded the bone, while, 5.7% invaded the skin layer. Survival analysis found that 44.3% of patients experienced relapse within two years postoperatively and the mortality rate after relapse was 75.9%. Almost 60.0% of the tumors involving the maxilla and/or mandible developed relapse. Cox proportional hazards model found that pN stage (p= 0.002) and bone invasion (p= 0.007) were significant independent predictors of 2-year disease-free survival. Importantly, 63.1% of patients had postoperative (and postradiotherapy) complications/sequalae. It was noteworthy that 18 of 43 patients (41.9%) who implanted with titanium plates had hardware-related complications/sequalae, and the most of them were titanium plate exposure (61.1%). CONCLUSIONS: Squamous cell carcinoma of the gingivobuccal complex cancer, as a new subsite worthy of attention in oral cancer, has a high complication/sequalae rate, high relapse rate and poor prognosis. TRIAL REGISTRATION: Prospective, Observational, Real-world Oral Malignant Tumors Study ( clinicaltrials.gov identifier: NCT02395367). The approval of the Institutional Review Board of the Beijing Stomatological Hospital of Capital Medical University (Approval number: CMUSH-IRB-KJPJ-2015-08).

From Plant to Yeast-Advances in Biosynthesis of Artemisinin.

Malaria is a life-threatening disease. Artemisinin-based combination therapy (ACT) is the preferred choice for malaria treatment recommended by the World Health Organization. At present, the main source of artemisinin is extracted from Artemisia annua; however, the artemisinin content in A. annua is only 0.1-1%, which cannot meet global demand. Meanwhile, the chemical synthesis of artemisinin has disadvantages such as complicated steps, high cost and low yield. Therefore, the application of the synthetic biology approach to produce artemisinin in vivo has magnificent prospects. In this review, the biosynthesis pathway of artemisinin was summarized. Then we discussed the advances in the heterologous biosynthesis of artemisinin using microorganisms (Escherichia coli and Saccharomyces cerevisiae) as chassis cells. With yeast as the cell factory, the production of artemisinin was transferred from plant to yeast. Through the optimization of the fermentation process, the yield of artemisinic acid reached 25 g/L, thereby producing the semi-synthesis of artemisinin. Moreover, we reviewed the genetic engineering in A. annua to improve the artemisinin content, which included overexpressing artemisinin biosynthesis pathway genes, blocking key genes in competitive pathways, and regulating the expression of transcription factors related to artemisinin biosynthesis. Finally, the research progress of artemisinin production in other plants (Nicotiana, Physcomitrella, etc.) was discussed. The current advances in artemisinin biosynthesis may help lay the foundation for the remarkable up-regulation of artemisinin production in A. annua through gene editing or molecular design breeding in the future.

[Identification of miR160 family and their target genes in Rehmannia glutinosa in response to endophytic fungus GG22 infection].

This study aims to reveal the possible role of miR160 family in Rehmannia glutinosa in response to the infection of endophytic fungus Fusarium oxysporum GG22. Specifically, miR160 precursors and mature miR160 were retrieved from the small RNA database yielded by high-throughput sequencing. RNAfold was used to analyze the precursor structure, and DNAMAN and MEGA to analyze conservation and evolution of miR160 precursors and mature miR160. The target genes of miR160 were predicted and annotated, and the interaction was analyzed. Based on degradome sequencing, the target genes were further identified. The results showed that miR160 precursors had intact stem-loop structures. The precursor and mature sequences were conserved, particularly the 3 rd-16 th bases of the 5'-terminal. According to the phylogenetic tree, R. glutinosa had close evolutionary relationship with Arabidopsis thaliana, Oryza sativa, Salvia miltiorrhiza, and Sesamum indicum. A total of 22 target genes of miR160 were predicted and most of them were auxin response factor(ARF) genes. The target genes were involved in the Gene Ontology(GO) terms of biological processes, cellular components, and molecular functions. According to the degradome sequencing results, four target genes of miR160 were ARF(ARF18, ARF22) genes. R. glutinosa regulated its growth in response to the infection of endophytic fungus by changing the expression of miR160 and the target genes. qRT-PCR result of the differentially expressed rgl-miR160a and rgl-miR160a-3p was consistent with the sequencing result. This study clarifies the molecular mechanism of R. glutinosa in response to GG22 stress, laying a theoretical basis for the improvement and future research of R. glutinosa.

Low loss hollow-core antiresonant fiber with nested supporting rings.

A hollow-core antiresonant fiber (HC-ARF) with nested supporting rings (NSRs) is designed and simulated. The HC-ARF with NSRs has advantages and benefits of low loss, large bandwidth, simple structure and a well bending characteristic, in which confinement loss (CL) is ∼ 0.15 dB/km @ 1.55 µm and the bandwidth is ∼ 220 nm @ CL < 1 dB/km. The bending loss (BL) is lower than ∼ 1 dB/km @ bend radius rc > 24 mm at 1.55 µm. Therefore, the HC-ARF with NSRs has potential applications of data transmission, sensing, high power delivery and so on.

Single-polarization single-mode hollow-core photonic-bandgap fiber with thin slab waveguide.

A novel single-polarization single-mode hollow-core photonic bandgap fiber with thin slab waveguide (TSW) was designed and simulated. Single-polarization guidance is achieved by the high loss of a polarized fundamental mode (FM) induced by mode coupling with a higher-order TE/TM mode of TSW and low loss of another polarized FM. We achieve a polarization loss ratio ∼ 46.9 dB, birefringence Δn ∼ 2.4 × 10-4, loss ∼ 35.9 dB/km and minimum higher-order mode extinction ratio > 15 dB. Moreover, the performance could be maintained when the guidance wavelength λ = 1.44 ∼ 1.56 µm and bending radius rc > 9 mm. The proposed model will be suitable for application as resonator sensing paths of miniaturized resonator fiber optic gyroscopes, high-performance interferometers, fiber lasers, frequency metrology, quantum communications, and laser-based gas sensing, etc.

Photoacoustic spectral analysis at ultraviolet wavelengths for characterizing the Gleason grades of prostate cancer.

The diagnosis of aggressive prostate cancer (PCa) has relied on microscopic architectures, namely Gleason patterns, of tissues extracted through core biopsies. Technology capable of assessing the tissue architecture without tissue extraction will reduce the invasiveness of PCa diagnosis and improve diagnostic accuracy by allowing for more sampling locations. Our recently developed photoacoustic spectral analysis (PASA) has achieved quantification of tissue architectural heterogeneity interstitially. Taking advantage of the unique optical absorption of cell nuclei at ultraviolet (UV) wavelengths, this study investigated PASA at 266 nm for quantifying the tissue architecture heterogeneity in prostates. The results have shown significant differences among the normal, early cancer, and late cancer stages in mouse prostates ex vivo and in vivo (n=20, p<0.05). The study with human samples ex vivo has shown a correlation of 0.80 (n=11, p<0.05) between PASA quantification and pathologic diagnosis.

Towards Clinical Translation of LED-Based Photoacoustic Imaging: A Review.

Photoacoustic imaging, with the capability to provide simultaneous structural, functional, and molecular information, is one of the fastest growing biomedical imaging modalities of recent times. As a hybrid modality, it not only provides greater penetration depth than the purely optical imaging techniques, but also provides optical contrast of molecular components in the living tissue. Conventionally, photoacoustic imaging systems utilize bulky and expensive class IV lasers, which is one of the key factors hindering the clinical translation of this promising modality. Use of LEDs which are portable and affordable offers a unique opportunity to accelerate the clinical translation of photoacoustics. In this paper, we first review the development history of LED as an illumination source in biomedical photoacoustic imaging. Key developments in this area, from point-source measurements to development of high-power LED arrays, are briefly discussed. Finally, we thoroughly review multiple phantom, ex-vivo, animal in-vivo, human in-vivo, and clinical pilot studies and demonstrate the unprecedented preclinical and clinical potential of LED-based photoacoustic imaging.

[Transcriptome analysis reveals genes involved in biosynthesis of secondary metabolism in Cornus officinalis].

In order to explore genetic basis for the biosynthesis of secondary metabolism,the transcriptome of Cornus officinalis was sequenced by the new generation of high-throughput sequencing technology,A total of 96 032 unigenes were assembled with an average length of 590.53 bp. Among them, 35 478 unigenes were annotated in the public databases NR,Swissprot,COG,GO,KOG,Pfam and KEGG. Based on the assignment of KEGG pathway, 84 involved in ridoid biosynthesis and 487 unigenes involved in others secondary metabolites biosynthesis were found. Additionally,53 unigenes and 72 unigenes were predicted to have potential functions of cytochome P450 and UDP- glycosyltransferases based on the annotation result, which may encode responsible for secondary metabolites modification. This study was the first comprehensive transcriptome analysis for C. officinalis, and the candidate genes involved in the biosynthesis of secondary metabolites were obtained. The transcriptome data constitutes a much more abundant genetic resource that can be utilized to benefit further molecular biology studies on C. officinalis.

[Cloning and Expression Analysis of Acetyl-CoA C-acetyltransferase Gene in Isodon rubescens].

Objective: To clone the acetyl-CoA C-acetyl transferase( AACT) gene from Isodon rubescens, and to analyze the bioinformatics and expression of the gene. Methods: According to the IrAACT gene sequence of Isodon rubescens transcriptome,a pair of primers was designed, and the ORF of cDNA sequence was obtained by reverse transcription PCR. Bioinformatic analysis of this gene and its corresponding protein were performed. Real-time quantitative PCR( q PCR) was used to detect the relative expression levels of IrAACT different tissues of Isodon rubescens. Results: The IrAACT cDNA sequence contained a 1 254 bp open reading frame and encoded a predicted protein of 417 amino acids. IrAACT had extensive homology with AACTs from other plant species, such as Salvia miltiorrhiza, et al. Bioinformatic analysis showed that IrAACT-encoding protein contained the thiolase Ⅱ catalytic domain. q PCR analysis showed that the expression of IrAACT was tissue-specific, and accumulation of transcripts was greater in flowers and leaves, followed by stems, roots and callus. Conclusion: It is the first time to report IrAACT gene and its relative expression level. The results will provide a groundwork for studying the function of IrAACT in terpenoid biosynthesis of Isodon rubescens.

Penicillium polonicum-mediated green synthesis of silver nanoparticles: Unveiling antimicrobial and seed germination advancements.

Silver nanoparticles (AgNPs), widely recognized for their nanoscale geometric size and unique properties, such as large specific surface area, high permeability, and high safety, were synthesized using the endophytic fungus Penicillium polonicum PG21 through a green approach. Four key synthesis factors-48 h, 45 °C, pH 9.0, and 80 mM AgNPs concentration-were optimized. Characterization via ultraviolet-visible spectroscopy, transmission electron microscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction revealed the AgNPs as approximately 3-25 nm spherical particles with numerous functional groups ensuring stability. AgNPs were tested against various fungal and bacterial plant pathogens, including Botrytis cinerea (EB-1), Alternaria alternata (EB-2, EB-3), Fusarium solani (RG-1), Williamsia serinedens (SL-1), Sphingopyxis macrogoltabida (SL-2), Bacillus velezensis (SL-3), and Pseudomonas mediterranea (SL-4), causing agricultural challenges. PG21-synthesized AgNPs exhibited inhibition rates against all tested fungi, with 60 µg/mL AgNPs demonstrating optimal inhibition rates. Notably, EB-1 experienced a significant growth inhibition, reaching an inhibition rate reached of 74.22 ± 1.54%. Conversely, RG-1 exhibited the smallest inhibitory effect at 48.13 ± 0.92%. The effect of AgNPs on safflower seed germination and growth revealed notable increases in shoot length, fresh weight, stem length, and number of lateral roots-1.4, 1.4, 1.33, and 10.67 times higher than the control, respectively, at an AgNPs concentration of 80 µg/mL. In conclusion, green-synthesized AgNPs demonstrate pathogen toxicity, showcasing potential applications in disease management for industrial crops and promoting plant growth.

A chromosome-level genome assembly and annotation of the medicinal plant Lepidium apetalum.

OBJECTIVES: As a traditional Chinese medicine, Lepidium apetalum is commonly used for purging the lung, relieving dyspnea, alleviating edema, and has the significant pharmacological effects on cardiovascular disease, hyperlipidemia, etc. In addition, the seeds of L. apetalum are rich in unsaturated fatty acids, sterols, glucosinolates and have a variety of biological activity compounds. To facilitate genomics, phylogenetic and secondary metabolite biosynthesis studies of L. apetalum, we assembled the high-resolution genome of L. apetalum. DATA DESCRIPTION: We completed chromosome-level genome assembly of the L. apetalum genome (2n = 32), using Illumina HiSeq and PacBio Sequel sequencing platform as well as high-throughput chromosome conformation capture (Hi-C) technique. The assembled genome was 296.80 Mb in size, 34.41% in GC content, and 23.89% in repeated sequence content, including 316 contigs with a contig N50 of 16.31 Mb. Hi-C scaffolding resulted in 16 chromosomes occupying 99.79% of the assembled genome sequences. A total of 46 584 genes and 105 pseudogenes were predicted, 98.37% of which can be annotated to Nr, GO, KEGG, TrEMBL, SwissPort, Pfam and KOG databases. The high-quality reference genome generated by this study will provide accurate genetic information for the molecular biology research of L. apetalum.

Photoacoustic imaging of squirrel monkey cortical responses induced by peripheral mechanical stimulation.

Non-human primates (NHPs) are crucial models for studies of neuronal activity. Emerging photoacoustic imaging modalities offer excellent tools for studying NHP brains with high sensitivity and high spatial resolution. In this research, a photoacoustic microscopy (PAM) device was used to provide a label-free quantitative characterization of cerebral hemodynamic changes due to peripheral mechanical stimulation. A 5 × 5 mm area within the somatosensory cortex region of an adult squirrel monkey was imaged. A deep, fully connected neural network was characterized and applied to the PAM images of the cortex to enhance the vessel structures after mechanical stimulation on the forelimb digits. The quality of the PAM images was improved significantly with a neural network while preserving the hemodynamic responses. The functional responses to the mechanical stimulation were characterized based on the improved PAM images. This study demonstrates capability of PAM combined with machine learning for functional imaging of the NHP brain.

A comparative proteomic analysis of Pinellia ternata leaves exposed to heat stress.

Pinellia ternata is an important traditional Chinese medicinal plant. The growth of P. ternata is sensitive to high temperatures. To gain a better understanding of heat stress responses in P. ternata, we performed a comparative proteomic analysis. P. ternata seedlings were subjected to a temperature of 38 °C and samples were collected 24 h after treatment. Increased relative ion leakage and lipid peroxidation suggested that oxidative stress was frequently generated in rice leaves exposed to high temperature. Two-dimensional electrophoresis (2-DE) was used to analyze heat-responsive proteins. More than 600 protein spots were reproducibly detected on each gel; of these spots, 20 were up-regulated, and 7 were down-regulated. A total of 24 proteins and protein species were successfully identified by MALDI-TOF/TOF MS. These proteins and protein species were found to be primarily small heat shock proteins (58%) as well as proteins involved in RNA processing (17%), photosynthesis (13%), chlorophyll biosynthetic processes (4%), protein degradation (4%) and defense (4%). Using 2-DE Western blot analysis, we confirmed the identities of the cytosolic class II small heat shock protein (sHSPs-CII) identified by MS. The expression levels of four different proteins [cytosolic class I small heat shock protein (sHSPs-CI), sHSPs-CII, mitochondrial small heat shock protein (sHSPs-MIT), glycine-rich RNA-binding protein (GRP)] were analyzed at the transcriptional level by quantitative real-time PCR. The mRNA levels of three sHSPs correlated with the corresponding protein levels. However, GRP was down-regulated at the beginning of heat stress but then increased substantially to reach a peak after 24 h of heat stress. Our study provides valuable new insight into the responses of P. ternata to heat stress.

In vivo monitoring of hemodynamic changes in ischemic stroke using photoacoustic tomography.

Ischemic stroke occurs when a blood vessel supplying the brain is blocked, leading to decreased blood flow. Early diagnosis and treatment are crucial. However, existing clinical imaging methods have limitations, such as safety issues and low time resolution. To address these challenges, we propose using photoacoustic tomography (PAT) with a contrast agent, known for its high resolution and contrast capabilities. Our study involved imaging brain vasculature in three groups: normal, unilateral common carotid artery ligation (UCAL), and middle cerebral artery occlusion (MCAO). On the ischemic stroke side, we observed reduced blood vessel density and hemodynamic changes were evident after injecting indocyanine green for PAT. The photoacoustic intensity was notably lower in the ligated sides of the UCAL and MCAO groups, with statistically significant differences between the three groups. This work highlights PAT's potential as a powerful tool for early diagnosis and guidance in ischemic stroke cases.