Characterization and Comparison of Contrast Imaging Properties of Naturally Isolated and Heterologously Expressed Gas Vesicles.

Nanoscale ultrasound contrast agents have attracted considerable interest in the medical imaging field for their ability to penetrate tumor vasculature and enable targeted imaging of cancer cells by attaching to tumor-specific ligands. Despite their potential, traditional chemically synthesized contrast agents face challenges related to complex synthesis, poor biocompatibility, and inconsistent imaging due to non-uniform particle sizes. To address these limitations, bio-synthesized nanoscale ultrasound contrast agents have been proposed as a viable alternative, offering advantages such as enhanced biocompatibility, consistent particle size for reliable imaging, and the potential for precise functionalization to improve tumor targeting. In this study, we successfully isolated cylindrical gas vesicles (GVs) from Serratia. 39006 and subsequently introduced the GVs-encoding gene cluster into Escherichia coli using genetic engineering techniques. We then characterized the contrast imaging properties of two kinds of purified GVs, using in vitro and in vivo methods. Our results demonstrated that naturally isolated GVs could produce stable ultrasound contrast signals in murine livers and tumors using clinical diagnostic ultrasound equipment. Additionally, heterologously expressed GVs from gene-engineered bacteria also exhibited good ultrasound contrast performance. Thus, our study presents favorable support for the application of genetic engineering techniques in the modification of gas vesicles for future biomedical practice.

Effect of clinical whole exome sequencing in aetiological investigation and reproductive risk prediction for a couple with monogenic inherited diseases.

Objective: To determine the genetic causes of monogenic inherited diseases in a couple using clinical whole exome sequencing (WES) and advise on their reproductive choices. Methods: WES was applied to a couple seeking reproductive advice, the female with short stature and the male with congenital cataracts. Results: (1) The woman exhibited a 13.8 Kb heterozygous deletion at chrX: 591590-605428 (hg19). This region corresponds to exons 2-6 of the short-stature homeobox-containing (SHOX) gene (NM000451). Associated diseases involving the SHOX gene range from severe Leri-Weill dyschondrosteosis to mild nonspecific short stature. Meanwhile, further validation using a quantitative reverse transcription polymerase chain reaction assay confirmed the heterozygous deletion of the SHOX gene in the proband, as well as other family members with similar clinical characteristics (the proband's mother, aunt, and cousin). Multiple pathogenic reports of this variant have been included in the HGMD database. Per the American College of Medical Genetics and Genomics (ACMG) classification criteria, this deletion is classified as pathogenic. (2) For the male patient, a heterozygous variant was detected in the CRYBB3 gene: NM004076: c.226G>A (p.Gly76R). Variants in the CRYBB3 gene can cause Cataract 22 (OMIM: 609741). At present, this variant locus is not included in databases such as the gnomAD, while both SIFT and PolyPhen2 deem this locus 'damaging'. Moreover, further validation by Sanger sequencing confirmed that the variant was inherited from the male patient's mother, who also had cataracts. According to ACMG standards and guidelines, the c.226G>A (p.Gly76Arg) variant in the CRYBB3 gene is classified as having 'uncertain significance'. Conclusion: WES identified pathogenic variants in both individuals, suggesting a 25% chance of a healthy child naturally. Third-generation assisted reproductive techniques are recommended to minimize the risk of affected offspring.

Isolation and Identification of Postharvest Rot Pathogens in Citrus × tangelo and Their Potential Inhibition with Acidic Electrolyzed Water.

This study focused on the identification of rot-causing fungi in Citrus × tangelo (tangelo) with a particular emphasis on investigating the inhibitory effects of acidic electrolyzed water on the identified pathogens. The dominant strains responsible for postharvest decay were isolated from infected tangelo fruits and characterized through morphological observation, molecular identification, and pathogenicity detection. Two strains were isolated from postharvest diseased tangelo fruits, cultured and morphologically characterized, and had their gene fragments amplified using primers ITS1 and ITS4. The results revealed the rDNA-ITS sequence of two dominant pathogens were 100% homologous with those of Penicillium citrinum and Aspergillus sydowii. These isolated fungi were confirmed to induce tangelo disease, and subsequent re-isolation validated their consistency with the inoculum. Antifungal tests demonstrated that acidic electrolyzed water (AEW) exhibited a potent inhibitory effect on P. citrinum and A. sydowii, with EC50 values of 85.4 µg/mL and 60.12 µg/mL, respectively. The inhibition zones of 150 µg/mL AEW to 2 kinds of pathogenic fungi were over 75 mm in diameter. Furthermore, treatment with AEW resulted in morphological changes such as bending and shrinking of the fungal hyphae surface. In addition, extracellular pH, conductivity, and absorbance at 260 nm of the fungi hypha significantly increased post-treatment with AEW. Pathogenic morphology and IST sequencing analysis confirmed P. citrinum and A. sydowii as the primary pathogenic fungi, with their growth effectively inhibited by AEW.

Elucidating the photodegradation mechanism of octylisothiazolinone and dichlorooctylisothiazolinone in surface water: An in-depth comprehensive analysis.

Octylisothiazolinone (OIT) and Dichlorooctylisothiazolinone (DCOIT), widely used antibacterial agents in coatings, have seen a sharp increase in use in response to the Coronavirus disease 2019 (Covid-19) pandemic, ultimately leading to their increase in the aquatic environment. However, their photodegradation process in surface water is still unclear. The purpose of this study is to investigate the photodegradation kinetics and mechanisms of OIT and DCOIT in natural water environments. Under simulated solar irradiation, they undergo direct photolysis in both natural freshwater and seawater mainly via their excited singlet states, while no self-sensitization photolysis was observed. The direct photolysis rate constants of OIT and DCOIT were 1.19 ± 0.07 and 0.57 ± 0.03 h-1, respectively. In addition, dissolved organic matter (DOM), NO3- and Cl- in natural waters did not contribute significantly to the photodegradation, and the light screening effect of DOM was identified as the main inhibiting factor. The photodegradation half-life of OIT was estimated to be 0.66 to 1.69 days, while the half-life of DCOIT was as high as 20.9 days during winter in surface water at 30°N latitude. Ring opening of the N-S bond and covalent bond breaking between CN are the main pathways for the photodegradation of OIT and DCOIT, which is verified by density-functional theory calculations. Ecological Structure Activity Relationships (ECOSAR) results indicate that OIT and DCOIT have "Very Toxic" biological toxicity, and the acute toxicity of their products is significantly reduced. It is noteworthy that the toxicity of the products of DCOIT is generally higher than that of OIT, and the chronic toxicity of most of the products is still above the "Toxic" level. Therefore, an in-depth understanding of the photodegradation mechanisms of OIT and DCOIT in aqueous environments is crucial for accurately assessing their ecological risks in natural water environments.

SAMP: Identifying Antimicrobial Peptides by an Ensemble Learning Model Based on Proportionalized Split Amino Acid Composition.

It is projected that 10 million deaths could be attributed to drug-resistant bacteria infections in 2050. To address this concern, identifying new-generation antibiotics is an effective way. Antimicrobial peptides (AMPs), a class of innate immune effectors, have received significant attention for their capacity to eliminate drug-resistant pathogens, including viruses, bacteria, and fungi. Recent years have witnessed widespread applications of computational methods especially machine learning (ML) and deep learning (DL) for discovering AMPs. However, existing methods only use features including compositional, physiochemical, and structural properties of peptides, which cannot fully capture sequence information from AMPs. Here, we present SAMP, an ensemble random projection (RP) based computational model that leverages a new type of features called Proportionalized Split Amino Acid Composition (PSAAC) in addition to conventional sequence-based features for AMP prediction. With this new feature set, SAMP captures the residue patterns like sorting signals at around both the N-terminus and the C-terminus, while also retaining the sequence order information from the middle peptide fragments. Benchmarking tests on different balanced and imbalanced datasets demonstrate that SAMP consistently outperforms existing state-of-the-art methods, such as iAMPpred and AMPScanner V2, in terms of accuracy, MCC, G-measure and F1-score. In addition, by leveraging an ensemble RP architecture, SAMP is scalable to processing large-scale AMP identification with further performance improvement, compared to those models without RP. To facilitate the use of SAMP, we have developed a Python package freely available at https://github.com/wan-mlab/SAMP.

Case Report: Right aortic arch with isolation of left brachiocephalic artery and ventricular septal defect.

Right aortic arch with isolation of left brachiocephalic artery is a rare congenital aortic arch anomaly. Herein, we reported a case of this rare anomaly with ventricular septal defect in a 9-month-old infant. We successfully reconstructed the islolated left brachiocephalic artery and repaired the ventricular septal defect in one stage.

A Review for Artificial Intelligence Based Protein Subcellular Localization.

Proteins need to be located in appropriate spatiotemporal contexts to carry out their diverse biological functions. Mislocalized proteins may lead to a broad range of diseases, such as cancer and Alzheimer's disease. Knowing where a target protein resides within a cell will give insights into tailored drug design for a disease. As the gold validation standard, the conventional wet lab uses fluorescent microscopy imaging, immunoelectron microscopy, and fluorescent biomarker tags for protein subcellular location identification. However, the booming era of proteomics and high-throughput sequencing generates tons of newly discovered proteins, making protein subcellular localization by wet-lab experiments a mission impossible. To tackle this concern, in the past decades, artificial intelligence (AI) and machine learning (ML), especially deep learning methods, have made significant progress in this research area. In this article, we review the latest advances in AI-based method development in three typical types of approaches, including sequence-based, knowledge-based, and image-based methods. We also elaborately discuss existing challenges and future directions in AI-based method development in this research field.

The effects of combined acupuncture anesthesia and serratus anterior plane block with ropivacaine on postoperative analgesia in patients undergoing chest surgery.

OBJECTIVE: To investigate the effects of combined acupuncture anesthesia and ropivacaine on postoperative analgesia and neuro-related factors in patients undergoing chest surgery. METHODS: The analgesic drug dosage, postoperative PCIA pressing times, VAS scores at rest and during activity at 6 h (T1), 12 h (T2), 18 h (T3), and 24 h (T4) postoperatively. RESULTS: The analgesic drug dosage and postoperative PCIA pressing times were lower in the observation group than in the control group (p < 0.05). The VAS scores at T1-T4 postoperatively were lower in the observation group than in the control group (p < 0.05). The SAS scores at T1-T4 postoperatively were lower in the observation group than in the control group (p < 0.05). The levels of IL-6 and IL-10 on postoperative day 1 were higher than those on preoperative day 1 in both groups, with a smaller change in the observation group (p < 0.05). The levels of S100ß protein on postoperative day 1 were higher than those on preoperative day 1 in both groups, while the BDNF levels were lower, with a smaller change in the observation group (p < 0.05). There was no significant difference in the incidence of adverse reactions between the control group (11.36%) and the observation group (15.56%) (p > 0.05). CONCLUSION: Combined acupuncture anesthesia and ropivacaine can effectively improve postoperative analgesia and agitation in patients undergoing chest surgery, reduce the dosage of analgesic drugs, regulate the levels of inflammatory factors and neurotrophic factors in patients, and do not increase the risk of adverse reactions related to patients.

Photochemical fate of ß-blocker pindolol in riverine and its downstream coastal waters.

Pindolol (PIN) is a commonly used ß-blocker drug and has been frequently detected in various natural waters. Comprehensive understanding of its environmental photochemical transformation is necessary to assess its environmental risk. In this study, the photodegradation kinetics and mechanisms of PIN in both freshwater and coastal water were investigated for the first time. The photodegradation experiments were carried out by steady-state photochemical experiment under simulated sunlight irradiation. The results showed that the photodegradation rate of PIN in the freshwater of the Pearl River estuary was significantly faster than that in its downstream coastal water. In river water, PIN can undergo both direct photolysis and indirect photolysis induced by riverine dissolved organic matter (DOM) mainly through excited triplet-state of DOM and singlet oxygen, while direct photolysis dominated its degradation in coastal water. The promotion effect was found to be much greater for Suwannee River Natural Organic Matter (SRNOM) than that of the sampled riverine DOM, due to its high steady-state concentrations of reactive species. Interestingly, coastal DOM in northern and southern China were found to have similar promotion effects on PIN photodegradation for the first time, but both less than that of riverine DOM. A total of seven degradation products of PIN resulting from hydroxylation, hydrogen abstraction and cleavage of ether bond were identified. Biological toxicity of one products were found to be higher than that of PIN. These results are of significance for knowing the persistence and ecological risk of PIN in natural waters.

Genetic Modulation of Biosynthetic Gas Vesicles for Ultrasound Imaging.

Gas vesicles (GVs) from microorganisms are genetically air-filled protein nanostructures, and serve as a new class of nanoscale contrast agents for ultrasound imaging. Recently, the genetically encoded GV gene clusters have been heterologously expressed in Escherichia coli, allowing these genetically engineered bacteria to be visualized in vivo in a real-time manner by ultrasound. However, most of the GV genes remained functionally uncharacterized, which makes it difficult to regulate and modify GVs for broad medical applications. Here, the impact of GV proteins on GV formation is systematically investigated. The results first uncovered that the deletions of GvpR or GvpU resulted in the formation of a larger proportion of small, biconical GVs compared to the full-length construct, and the deletion of GvpT resulted in a larger portion of large GVs. Meanwhile, the combination of gene deletions has resulted in several genotypes of ultrasmall GVs that span from 50 to 20 nm. Furthermore, the results showed that E. coli carrying the ΔGvpCRTU mutant can produce strong ultrasound contrast signals in mouse liver. In conclusion, the study provides new insights into the roles of GV proteins in GV formation and produce ultrasmall GVs with a wide range of in vivo research.

Photo-production of excited triplet-state of dissolved organic matters in inland freshwater and coastal seawater.

The excited triplet-state of dissolved organic matter (3DOM*) is a major reactive intermediate in sunlit waters. Its quantum yield is important in understanding the fate of organic micropollutants. The degradation efficiency of its chemical probe, 2,4,6-trimeythlphenol (fTMP), is generally used as a proxy of the quantum yield. However, fTMP has been described and modelled only for freshwater systems. Therefore, this study quantified fTMP in inland freshwater and coastal seawater sampled in Japan by conducting steady-state photochemical experiments. Optical properties of water were then used to model fTMP. Results indicated that the inland freshwater DOM originated mainly from terrestrial sources, while the coastal seawater DOM were microbial-dominated. On average, inland freshwater exhibited lower fTMP (61.2 M-1) than coastal seawater (79.7 M-1) and the coastal seawater exhibited significant variations in the proportion of high-energy 3DOM* (> 250 kJ/mol). In addition, E2:E3 (ratio of absorbance at 254 to 365 nm) was positively correlated with fTMP of inland freshwater, coastal seawater, and the overall dataset. Catchment conditions such as forest coverage also influenced the production of 3DOM* and high-energy 3DOM* in inland freshwater. Furthermore, the developed models estimated fTMP based on the optical properties of both freshwater and seawater, providing valuable insights about 3DOM* photochemistry in the aquatic environment.

Nanoscale contrast agents: A promising tool for ultrasound imaging and therapy.

Nanoscale contrast agents have emerged as a versatile platform in the field of biomedical research, offering great potential for ultrasound imaging and therapy. Various kinds of nanoscale contrast agents have been extensively investigated in preclinical experiments to satisfy diverse biomedical applications. This paper provides a comprehensive review of the structure and composition of various nanoscale contrast agents, as well as their preparation and functionalization, encompassing both chemosynthetic and biosynthetic strategies. Subsequently, we delve into recent advances in the utilization of nanoscale contrast agents in various biomedical applications, including ultrasound molecular imaging, ultrasound-mediated drug delivery, and cell acoustic manipulation. Finally, the challenges and prospects of nanoscale contrast agents are also discussed to promote the development of this innovative nanoplatform in the field of biomedicine.

Tripartite motif-containing protein 26 promotes colorectal cancer growth by inactivating p53.

Tripartite motif-containing protein 26 (TRIM26) is an E3 ubiquitin ligase that exhibits divergent roles in various cancer types (oncogenic and anti-oncogenic). This study investigates the interaction of TRIM26 with the tumor suppressor protein p53 in colorectal cancer (CRC) cells by performing a comprehensive set of biochemical, cell-based assays, and xenograft experiments. As a result, we found that overexpression of TRIM26 significantly enhances CRC cell proliferation and colony formation, while knockdown of TRIM26 suppresses these processes. Xenograft experiments further validated the tumor-promoting role of TRIM26 in CRC. Supporting this is that TRIM26 is highly expressed in human CRC tissues as revealed by our analysis of the TCGA database. Biochemically, TRIM26 directly bound to the C-terminus of p53 and facilitated its ubiquitination, resulting in proteolytic degradation and attenuated p53 activity independently of MDM2. Also, TRIM26 increased the MDM2-mediated ubiquitination of p53 by binding to MDM2's C-terminus. This study uncovers the oncogenic potential of TRIM26 in CRC by inhibiting p53 function. Through its ubiquitin ligase activity, TRIM26 destabilizes p53, consequently promoting CRC cell proliferation and tumor growth. These findings shed light on the complex involvement of TRIM26 in cancer and identify this ubiquitin ligase as a potential therapeutic target for future development of CRC treatment.

Effect of the type of brewing water on the sensory and physicochemical properties of light-scented and strong-scented Tieguanyin oolong teas.

Variations in the quality of brewing water profoundly impact tea flavor. This study systematically investigated the effects of four common water sources, including pure water (PW), mountain spring water (MSW), mineral water (MW) and natural water (NW) on the flavor of Tieguanyin tea infusion. Brewing with MW resulted in a flat taste and turbid aroma, mainly due to the low leaching of tea flavor components and complex interactions with mineral ions (mainly Ca2+, Mg2+). Tea infusions brewed with NW exhibited the highest relative contents of total volatile compounds, while those brewed with PW had the lowest. NW and MSW, with moderate mineralization, were conducive to improving the aroma quality of tea infusion and were more suitable for brewing both aroma types of Tieguanyin. These findings offer valuable insights into the effect of brewing water on the sensory and physicochemical properties of oolong teas.

Moisture content of tea dhool for the scenting process affects the aroma quality and volatile compounds of osmanthus black tea.

To improve the quality of osmanthus black tea, samples produced with different scenting methods were prepared. The sensory quality was assessed and the characteristic aromatic components were explored using solid-phase microextraction (SPME) coupled with gas chromatography-mass spectrometry. According to the results, osmanthus black tea obtained by adding osmanthus scenting in the fermentation process had the strongest floral aroma. The major contributors to the aroma of osmanthus black tea were identified as ß-ionone, dihydro-ß-ionone, benzeneacetaldehyde, citral, geraniol, and linalool by calculating their relative odor activity values. An analysis of the causes revealed that the moisture content of tea dhool significantly affected the adsorption of fresh flower aroma by tea. The experimental results showed that osmanthus black tea produced using tea dhool containing 30% moisture content had the highest content of crucial aroma components, suggesting the tea dhool under this condition had the strongest adsorption capacity for osmanthus aroma.

RNA-binding motif protein 10 inactivates c-Myc by partnering with ribosomal proteins uL18 and uL5.

RNA-binding motif protein 10 (RBM10) is a frequently mutated tumor suppressor in lung adenocarcinoma (LUAD). Yet, it remains unknown whether cancer-derived mutant RBM10 compromises its tumor suppression function and, if so, the molecular insight of the underlying mechanisms. Here, we show that wild-type RBM10 suppresses lung cancer cell growth and proliferation by inactivating c-Myc that is essential for cancer cell survival. RBM10 directly binds to c-Myc and promotes c-Myc's ubiquitin-dependent degradation, while RBM10 knockdown leads to the induction of c-Myc level and activity. This negative action on c-Myc is further boosted by ribosomal proteins (RPs) uL18 (RPL5) and uL5 (RPL11) via their direct binding to RBM10. Cancer-derived mutant RBM10-I316F fails to bind to uL18 and uL5 and to inactivate c-Myc, thus incapable of suppressing tumorigenesis. Our findings uncover RBM10 as a pivotal c-Myc repressor by cooperating with uL18 and uL5 in lung cancer cells, as its failure to do so upon mutation favors tumorigenesis.

Application of Copy Number Variation Sequencing Technology in 422 Foetuses with Abnormal Ultrasound Soft Markers.

Purpose: The application value of ultrasound soft indicators in prenatal diagnosis was evaluated by copy number variation sequencing (CNV-seq). Methods: The authors conducted a retrospective analysis of 422 pregnant women who underwent CNV-seq testing at Luoyang Maternal and Child Health Hospital between January 2020 and November 2021. The women had presented with abnormal ultrasound soft markers; those identified as high-risk through non-invasive prenatal screening were excluded. Results: A total of 43 abnormal cases were detected in 422 pregnant women, including 24 aneuploidy (including chimerism) and 19 pathogenic or likely pathogenic copy number variations (CNVs). Based on the characteristics of ultrasound soft indicators, pregnant women were divided into five groups: isolated nuchal translucency (NT) group, combined NT group, isolated soft indicators group, combined soft indicators group and combined non-NT group. The abnormality detection rates in the five groups were 12.38% (13/105), 36.11% (13/36), 3.74% (4/103), 3.08% (2/63) and 10.09% (11/109), respectively. Statistical tests showed that the detection rate in the NT thickening combined with other abnormalities group was significantly higher than the other four groups, while there was no statistical difference in the detection rate among the other four groups. Conclusion: When NT thickening is combined with other abnormalities, it is more likely to indicate chromosome abnormalities or CNVs, so it should be regarded seriously upon finding, and pregnant women should be referred for prenatal diagnosis according to the examination results. In addition, NT thickening is an important indicator for prenatal diagnosis and should be considered regardless of whether it occurs independently. The authors recommend CNV-seq for prenatal diagnosis to prevent missing small fragments of CNVs during traditional karyotyping.

Shuyu capsule alleviates premenstrual depression via allopregnanolone metabolic pathway targeting GABA (A) receptors δ subunit in the hippocampus.

To reveal the exact changes of allopregnanolone-mediated γ-aminobutyric acid A receptor pathways and its specific therapeutic targets by Shuyu Capsule treating premenstrual depression, female Wistar rat models of premenstrual depression was established by Forced swimming test (FST). Behavioral tests, enzyme-linked immunosorbent assay (ELISA), interference knockdown adenovirus, and overexpressed vector adenovirus of GABAARδ, RT-qPCR, Western-Blot, and immunohistochemical detecting expressions were applied to identify the therapeutic targets. FST-based rat model indicated that Shuyu capsules alleviated typical premenstrual depression and may regulate alternations of 5α-reductase and 3α-steroid dehydrogenase, enhancing the metabolic pathway of progesterone to allopregnanolone, as well as targeting the GABAARδ subunit, thereby alleviating premenstrual depression of PMDD rat models.

Insights into the mechanisms of natural organic matter on the photodegradation of indomethacin under natural sunlight and simulated light irradiation.

Indomethacin (INDO) is an antipyretic and analgesic pharmaceutical that has been widely detected in the aquatic environment. Photodegradation is an essential pathway for removal of INDO in sunlit surface water, however the effect of dissolved organic matter (DOM) on its photodegradation and the ecotoxicity of photodegradation products are largely unknown. In this study, the effect of DOM on the photodegradation of INDO under both natural and simulated light irradiation was studied. The results showed that indirect photolysis is the main photodegradation pathway of INDO in presence of DOM where 3DOM* plays the most important promoting role. Compared to commercial DOM (SRNOM and SRFA), DOM extracted from local-lake water (SLDOM) promoted the photodegradation to the highest extent. Although the steady-state concentrations of 3DOM* of SRNOM and SRFA were higher than SLDOM, their inhibition effect surpassed SLDOM namely higher light screening effect and phenolic antioxidant concentrations. The photodegradation pathway in pure water is different from that in DOM system where the decarboxylation of acetic acid chain and the oxidative fracture of indole ring are the main degradation pathways. Density Functional Theory (DFT) calculation further supports the proposed degradation pathways of INDO. ECOSAR calculation showed that the toxicity of INDO photodegradation products to aquatic organisms may maintain or even exceed its parent compound. Therefore, comprehensive understanding of the impact of DOM on the photodegradation of INDO is of crucial significance for evaluating its ecological risk in the natural environment.