Recent research on material-based methods for isolation of extracellular vesicles.

Extracellular vesicles (EVs) are nanoparticles secreted by cells with a closed phospholipid bilayer structure, which can participate in various physiological and pathological processes and have significant clinical value in disease diagnosis, targeted therapy and prognosis assessment. EV isolation methods currently include differential ultracentrifugation, ultrafiltration, size exclusion chromatography, immunoaffinity, polymer co-precipitation and microfluidics. In addition, material-based biochemical or biophysical approaches relying on intrinsic properties of the material or its surface-modified functionalized monomers, demonstrated unique advantages in the efficient isolation of EVs. In order to provide new ideas for the subsequent development of material-based EV isolation methods, this review will focus on the principle, research status and application prospects of material-based EV isolation methods based on different material carriers and functional monomers.

Carbon storage through China's planted forest expansion.

China's extensive planted forests play a crucial role in carbon storage, vital for climate change mitigation. However, the complex spatiotemporal dynamics of China's planted forest area and its carbon storage remain uncaptured. Here we reveal such changes in China's planted forests from 1990 to 2020 using satellite and field data. Results show a doubling of planted forest area, a trend that intensified post-2000. These changes lead to China's planted forest carbon storage increasing from 675.6 ± 12.5 Tg C in 1990 to 1,873.1 ± 16.2 Tg C in 2020, with an average rate of ~ 40 Tg C yr-1. The area expansion of planted forests contributed ~ 53% (637.2 ± 5.4 Tg C) of the total above increased carbon storage in planted forests compared with planted forest growth. This proactive policy-driven expansion of planted forests has catalyzed a swift increase in carbon storage, aligning with China's Carbon Neutrality Target for 2060.

Discovery of novel FUT8 inhibitors with promising affinity and in vivo efficacy for colorectal cancer therapy.

As a member of glycosyltransferases, fucosyltransferase 8 (FUT8) is essential to core fucosylation and has been considered as a potential therapeutic target for malignant tumors, including colorectal cancer (CRC). Based on the identification of key binding residues and probable conformation of FUT8, an integrated strategy that combines virtual screening and chemical optimization was carried out and compound 15 was identified as a potent FUT8 inhibitor with novel chemical structure and in vitro antitumor activity. Moreover, chemical pulldown experiments and binding assays confirmed that compound 15 selectively bound to FUT8. In vivo, compound 15 showed promising anti-CRC effects in SW480 xenografts. These data support that compound 15 is a potential FUT8 inhibitor for CRC treatment and deserve further optimization studies.

Cation-crosslinkedκ-carrageenan sub-microgel medium for high-quality embedded bioprinting.

Three-dimensional (3D) bioprinting embedded within a microgel bath has emerged as a promising strategy for creating intricate biomimetic scaffolds. However, it remains a great challenge to construct tissue-scale structures with high resolution by using embedded 3D bioprinting due to the large particle size and polydispersity of the microgel medium, as well as its limited cytocompatibility. To address these issues, novel uniform sub-microgels of cell-friendly cationic-crosslinked kappa-carrageenan (κ-Car) are developed through an easy-to-operate mechanical grinding strategy. Theseκ-Car sub-microgels maintain a uniform submicron size of around 642 nm and display a rapid jamming-unjamming transition within 5 s, along with excellent shear-thinning and self-healing properties, which are critical for the high resolution and fidelity in the construction of tissue architecture via embedded 3D bioprinting. Utilizing this new sub-microgel medium, various intricate 3D tissue and organ structures, including the heart, lungs, trachea, branched vasculature, kidney, auricle, nose, and liver, are successfully fabricated with delicate fine structures and high shape fidelity. Moreover, the bone marrow mesenchymal stem cells encapsulated within the printed constructs exhibit remarkable viability exceeding 92.1% and robust growth. Thisκ-Car sub-microgel medium offers an innovative avenue for achieving high-quality embedded bioprinting, facilitating the fabrication of functional biological constructs with biomimetic structural organizations.

Discovery and Development of 4-Hydroxyphenylpyruvate Dioxygenase as a Novel Crop Fungicide Target.

Plant pathogenic fungi pose a significant threat to crop yields and quality, and the emergence of fungicide resistance has further exacerbated the problem in agriculture. Therefore, there is an urgent need for efficient and environmentally friendly fungicides. In this study, we investigated the antifungal activity of (+)-Usnic acid and its inhibitory effect on crop pathogenic fungal 4-hydroxyphenylpyruvate dioxygenases (HPPDs) and determined the structure of Zymoseptoria tritici HPPD (ZtHPPD)-(+)-Usnic acid complex. Thus, the antifungal target of (+)-Usnic acid and its inhibitory basis toward HPPD were uncovered. Additionally, we discovered a potential lead fungicide possessing a novel scaffold that displayed remarkable antifungal activities. Furthermore, our molecular docking analysis revealed the unique binding mode of this compound with ZtHPPD, explaining its high inhibitory effect. We concluded that HPPD represents a promising target for the control of phytopathogenic fungi, and the new compound serves as a novel starting point for the development of fungicides and dual-purpose pesticides.

Structure-based discovery of pyrazole-benzothiadiazole hybrid as human HPPD inhibitors.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) has attracted increasing attention as a target for treating type I tyrosinemia and other diseases with defects in tyrosine catabolism. Only one commercial drug, 2-(2-nitro-4-trifluoromethylbenzoyl)-1, 3-cyclohexanedione (NTBC), clinically treat type I tyrosinemia, but show some severe side effects in clinical application. Here, we determined the structure of human HPPD-NTBC complex, and developed new pyrazole-benzothiadiazole 2,2-dioxide hybrids from the binding of NTBC. These compounds showed improved inhibition against human HPPD, among which compound a10 was the most active candidate. The Absorption Distribution Metabolism Excretion Toxicity (ADMET) predicted properties suggested that a10 had good druggability, and was with lower toxicity than NTBC. The structure comparison between inhibitor-bound and ligand-free form human HPPD showed a large conformational change of the C-terminal helix. Furthermore, the loop 1 and α7 helix were found adopting different conformations to assist the gating of the cavity, which explains the gating mechanism of human HPPD.

One-pot preparation of bi-functional POSS-based hybrid monolith via photo-initiated polymerization for isolation of extracellular vesicles.

Extracellular vesicles (EVs) are important participants in numerous pathophysiological processes, and could be used as valuable biomarkers to detect and monitor various diseases. However, facile EV isolation methods are the essential and preliminary issue for their downstream analysis and function investigation. In this work, a polyhedral oligomeric silsesquioxanes (POSS) based hybrid monolith combined metal affinity chromatography (MAC) and distearoyl phospholipid ethanolamine (DSPE) function was developed via photo-initiated thiol-ene polymerization. This synthesis process was facile, simple and convenient, and the obtained hybrid monolith could be applied to efficiently isolate EVs from bio-samples by taking advantages of the specific bond of Ti4+ and phosphate groups on the phospholipid membrane of EVs and the synergistic effect of DSPE insertion. Meanwhile, the eluted EVs could maintain their structural integrity and biological activity, suggesting they could be used for downstream application. Furthermore, 75 up-regulated proteins and 56 down-regulated proteins were identified by comparing the urinary EVs of colorectal cancer (CRC) patients and healthy donors, and these proteins might be used as potential biomarkers for early screening of CRC. These results demonstrated that this hybrid monolith could be used as a simple and convenient tool for isolating EVs from bio-samples and for wider applications in biomarker discovery.

Conservative management of double teeth in molar teeth with pulp or periapical disease: a report of five cases and literature review.

BACKGROUND: Double teeth are usually the result of an abnormality in the developing tooth germ. Double teeth can occur in either the primary or permanent dentition, with the majority of cases concerning permanent teeth reported in the anterior teeth and less frequently in the molar teeth. CASE PRESENTATION: This report illustrates five cases of double teeth in molars with pulp and periapical disease, including one case of geminated teeth and four cases of fused teeth. Radiographic findings revealed the presence of extra teeth on the buccal aspect of the molar in five cases, with or without communication between the two root canal systems. Root canal treatment was performed by using CBCT and a dental operating microscope. The treatment outcome was good in all five cases. CONCLUSION: The diagnosis and treatment of double teeth requires special attention. The root canal system should be carefully explored to obtain a full understanding of the anatomy, allowing it to be fully cleaned and obturated. Proper anatomical structure analysis prior to treatment facilitates the development of an appropriate treatment plan, thereby increasing the likelihood of successful treatment both aesthetically and functionally.

FDW028, a novel FUT8 inhibitor, impels lysosomal proteolysis of B7-H3 via chaperone-mediated autophagy pathway and exhibits potent efficacy against metastatic colorectal cancer.

Metastatic colorectal cancer (mCRC) is a major cause of cancer-related mortality due to the absence of effective therapeutics. Thus, it is urgent to discover new drugs for mCRC. Fucosyltransferase 8 (FUT8) is a potential therapeutic target with high level in most malignant cancers including CRC. FUT8 mediates the core fucosylation of CD276 (B7-H3), a key immune checkpoint molecule (ICM), in CRC. FUT8-silence-induced defucosylation at N104 on B7-H3 attracts heat shock protein family A member 8 (HSPA8, also known as HSC70) to bind with 106-110 SLRLQ motif and consequently propels lysosomal proteolysis of B7-H3 through the chaperone-mediated autophagy (CMA) pathway. Then we report the development and characterization of a potent and highly selective small-molecule inhibitor of FUT8, named FDW028, which evidently prolongs the survival of mice with CRC pulmonary metastases (CRPM). FDW028 exhibits potent anti-tumor activity by defucosylation and impelling lysosomal degradation of B7-H3 through the CMA pathway. Taken together, FUT8 inhibition destabilizes B7-H3 through CMA-mediated lysosomal proteolysis, and FDW028 acts as a potent therapeutic candidate against mCRC by targeting FUT8. FDW028, an inhibitor specifically targeted FUT8, promotes defucosylation and consequent HSC70/LAMP2A-mediated lysosomal degradation of B7-H3, and exhibits potent anti-mCRC activities.

Research on the Frontier and Prospect of Service Robots in the Tourism and Hospitality Industry Based on International Core Journals: A Review.

This paper used the mixed research method of bibliometric and content analysis to study 284 studies on service robots in the tourism and hospitality industry collected from the Web of Science database. Results show that research in this field started late, and that the COVID-19 pandemic has promoted the rapid growth of the number of research papers. The International Journal of Contemporary Hospitality Management has so far published the most number of papers. Numerous scholars from universities in different regions of the world have made significant contributions to the research of service robots, and academic collaborations are relatively common, but there are only very few high-yield authors. Empirical research has been widely favored by researchers, wherein online questionnaire and experimental methods have been frequently used. Multidisciplinary theories have also been cited in related articles, especially on the applications of psychological theories. The research fronts cover four branches focusing on service robots, consumers, human employees, and service environment, with all four parts largely overlapping in content. Finally, the paper discusses prospects for the future research agenda of service robots in the tourism and hospitality industry.

Expression and clinicopathological characteristics of PDX1, PTF1A, and SALL4 in large and small ducts of ectopic pancreas located in gastro-duodenum and jejunum.

An ectopic pancreas is defined as pancreatic tissue outside its normal location, anatomically separated from the pancreas. The transcription factor pancreas/duodenum homeobox protein 1 (PDX1) is involved in maintaining the pancreas and functions in early pancreatic development, beta cell differentiation, and endocrine non beta cells. Pancreatic transcription factor 1 subunit alpha (PTF1A) affects exocrine cell formation and regulation of acinar cell identity, and is expressed in exocrine cells as a transcription factor. The depletion of SALL4 disrupts self-renewal and induces differentiation. To clarify which of PDX1, PTF1A, or SALL4 determines the difference in Heinrich's classification, we examined the localization and number of positive cells. We analyzed the differential expression of PDX1, PTF1A, and SALL4 in large and small ducts in ectopic pancreas by immunohistochemistry. Results showed that the number of PTF1A-positive cells in large ducts was more widespread in type I than in type II in the gastro-duodenum, and more SALL4-positive cells were noticed in large ducts than in small ducts in the gastro-duodenum of type II. Our results revealed that PTF1A might promote exocrine differentiation in developing the pancreatic tissues, and that those with widespread expression differentiate into exocrine cells.

Ti3C2 and Ti2C MXene materials for high-performance isolation of extracellular vesicles via coprecipitation.

Two-dimensional (2D) materials such as MXenes, are usually well utilized in the field of catalysts and battery due to their good hydrophilicity and diversified surface terminals. However, their potential applications in the treatment of biological samples have not been widely concerned. Extracellular vesicles (EVs) contain unique molecular signatures and could be used as biomarkers for the detection of severe diseases such as cancer, as well as monitoring the therapeutic response. In this work, two kinds of MXene materials (Ti3C2 and Ti2C) were successfully synthesized and employed in the isolation of EVs from the biological samples by taking advantage of the affinity interaction between the titanium (Ti) in MXenes and the phospholipid membrane of EVs. Compared with Ti2C MXene materials, TiO2 beads and the other EVs isolation methods, Ti3C2 MXene materials exhibited excellent isolation performance via the coprecipitation with EVs due to the abundant unsaturated coordination of Ti2+/Ti3+, and the dosage of materials was the lowest. Meanwhile, the whole isolation process could be done within 30 min and integrated well with the following analysis of proteins and ribonucleic acids (RNAs), which was also convenient and economic. Furthermore, the Ti3C2 MXene materials were used to isolate the EVs from the blood plasma of colorectal cancer (CRC) patients and healthy donors. Proteomics analysis of EVs showed that 67 proteins were up-regulated, in which most of them were closely related to CRC progression. These findings indicate that the MXene material-based EVs isolation method via coprecipitation provides an efficient tool for early diagnosis of diseases.

Choroidal blood perfusion could predict the sensitivity of myopia formation in Guinea pigs.

In this study, we explored the predictive role of choroidal blood perfusion (ChBP) and choroidal thickness (ChT) on the development of myopia in guinea pigs. Optical Coherence Tomography Angiography (OCTA) was used to assess the baseline choroidal blood perfusion (ChBP) and choroidal thickness (ChT) in 4-week-old guinea pigs. Refraction and axial length (AL) were measured at baseline. Myopia was induced for one week using form-deprivation (FD) or negative lenses followed by measurements of refraction, axial length and choroidal parameters (ChT and ChBP). The correlations were evaluated between the baseline choroidal values and the magnitude of myopia induced, along with the magnitude of changes in ChT and ChBP after myopia induction. There was a significant correlation between the baseline choroidal parameters and ocular refraction. Myopia induction led to choroidal thinning and less ChBP as well as longer eyes. On the other hand, following exposure to the same non-obstructed visual induction period, the myopic shift was less, and it was associated with thicker choroids and more ChBP at baseline. One week of myopia induction also resulted in thinner choroids and less ChBP, and these declines also correlated with their baseline values. In conclusion, the present study shows that the changes in the baseline choroidal ChT and ChBP parameters are proportional to the magnitude of myopia development and axial elongation in guinea pigs. These significant correlations between baseline ChBP and ChT and myopia development suggest that they may be a viable predictor of this process in guinea pigs.

A new neurosurgical adjustable pressure suction apparatus with a mechanically controlled air inlet: the study of precise regulation and atraumatic suction.

Background: An essential surgical tool in neurosurgery is the suction tube. The skillful and accurate use of a suction tube facilitates the neurosurgical operation. Objective: This study is to verify the practicality of an adjustable pressure suction tube (APS tube) and to explore the ideal APS tube diameter and tip negative pressure for different intracranial structures. Methods: APS tubes were used to aspirate brain tissues and carotid arteries of rats. Laser speckle contrast imaging (LSCI) was used to record the blood flow velocity (BFV). We measured APS tube diameter, air inlet size, tip negative pressure and central negative pressure and calculated the correlation between them. In our department, intraoperative real-time parameters including APS tube diameter, length, air inlet size, and central negative pressure were recorded, and the tube tip negative pressure suitable for different intracranial structures and parts was calculated. Results: All experiments were carried out using APS tubes. Experiments on rats objectively reflected a severe structural damage to the brain and blood vessels by the suction tube, which might even result in an irreversible reduction in blood flow., Rat carotid arteries and brain tissue suffered severe damage when the tip negative pressure exceeded 33.4 ± 1.8 and 29.2 ± 2.0 kPa, respectively. BFV failed to return to the preoperative level 3 min after the operation (p < 0.05), and this decrease was more pronounced when the suction tube diameter was large (p < 0.05). The tip negative pressure was positively and negatively correlated with central negative pressure and the air inlet size, and was independent of APS tube diameter. A total of 50 operations including 39 tumor resection operations and 11 moyamoya disease bypass operations were recorded. Large-diameter APS tubes (3.5 mm) with an closed air inlet were frequently used to maintain a greater tip negative pressure before the incision of dura mater. When important structures such as motor cortex and brainstem were involved, 1.5- or 2.0-mm-diameter APS tubes were mostly used, and an air inlet was opened up to 0.7-2.1 mm to maintain a safe tip negative pressure (7.4-27.9 kPa). Conclusion: APS tubes with a mechanical knob provide stable and precise adjustment of the tip negative pressure, avoiding excessive negative pressure that causes serious damage to the intracranial structure. And, this allows the surgeon to hold the suction tube more freely and operate at any angle with an appropriate fulcrum near the incision to achieve efficient atraumatic suction and enhance surgical safety.

Did the COVID-19 pandemic (really) positively impact the IPO Market? An Analysis of information uncertainty.

Anecdotal evidence seems to suggest that the initial public offering (IPO) market performed remarkably well through the COVID-19 pandemic. To further understand this peculiar observation, we carry out a comprehensive analysis of IPOs during the pandemic vis-a-vis IPOs before the pandemic. Our findings imply that IPOs during the pandemic experience greater information uncertainty compared to those before the pandemic, and this greater uncertainty is mainly driven by the IPOs from the high-technology and the healthcare sectors. Furthermore, we find that an average IPO firm experiences larger underpricing and more post-IPO return volatility as the pandemic and the associated government responses increase in severity before the offering. Overall, our study indicates that the COVID-19 pandemic had an adverse impact on the IPO market.

Synergistic antitumor activity of 5-fluorouracil and atosiban against microsatellite stable colorectal cancer through restoring GATA3.

Clinically, 5-fluorouracil (5-Fu) is a first-line drug for the treatment of patients with colorectal cancer (CRC). However, chemoresistance to 5-Fu-based chemotherapy is a leading obstacle in achieving effective treatment for CRC, especially microsatellite stable (MSS) CRC. Since the cytotoxicity of 5-Fu is negatively correlated with oxytocin receptor (OXTR) expression in MSS CRC cell lines, our current study aimed to investigate the synergistic antitumor activity of 5-Fu combined with atosiban, an antagonist of OXTR. Our results suggested that atosiban remarkably potentiated the inhibitory effect of 5-Fu on the growth of MSS-type CRC cells in vitro and in vivo. Moreover, 5-Fu induced GATA3 in MSS CRC cells and tumors, which were eradicated by atosiban. Further investigation showed that atosiban strengthened the antitumor activity of 5-Fu through eradiation of 5-Fu-induced GATA3 in MSS-type CRC cells. Taken together, our findings suggest that atosiban potentiates the antitumor effect of 5-Fu by abolishing 5-Fu-induced GATA3, which provides a novel therapeutic strategy for MSS-type CRC via the combination of atosiban and 5-Fu.

Microsatellite Instability Analysis and Its Prognostic Value in Invasive Nonampullary Duodenal Adenocarcinoma.

PURPOSE: Nonampullary duodenal adenocarcinoma (NADA) is a rare disease. Although several prognostic factors have been reported for this disease, they remain controversial due to their rarity. In this study, we retrospectively analyzed 54 cases of invasive NADA, focusing on the microsatellite instability (MSI) phenotype, programmed cell death-ligand 1 (PD-L1) expression, and prognostic factors. METHODS: Expression of the PD-L1 protein and cell differentiation markers in tumors was detected by immunohistochemistry. Microsatellite markers (NR-21, NR-22, NR-24, BAT-25, and BAT-26) were amplified for MSI assessment by PCR. RESULTS: The incidence of MSI in invasive NADA was 35.2%. No significant correlation between the MSI phenotype and clinicopathological factors was observed. Positive expression of PD-L1 by immune cells was common in advanced-stage disease (p = 0.054), and positive expression of PD-L1 in cancer cells correlated significantly with the histologically undifferentiated type (p = 0.016). Kaplan-Meier survival analysis demonstrated a significantly better overall survival (OS) in patients with MSI (p = 0.013) and at early-stage disease (p = 0.000) than in those with microsatellite-stable or at late tumor stages. Univariate and multivariate analyses showed that MSI (hazard ratio [HR]: 0.282, 95% confidence interval [CI]: 0.106-0.751, p = 0.011) and early tumor stage (stage I-II) (HR: 8.81, 95% CI: 2.545-30.500, p = 0.001) were independent better prognostic factors of OS. CONCLUSIONS: MSI and early tumor stage (stage I-II) were independent better prognostic factors of OS. A high proportion of MSI phenotypes and positive PD-L1 expression may be helpful for identifying immune checkpoint inhibitors as a novel therapeutic strategy.

Photoactivated DNA Walker Based on DNA Nanoflares for Signal-Amplified MicroRNA Imaging in Single Living Cells.

Specific and sensitive detection and imaging of cancer-related miRNA in living cells are desirable for cancer diagnosis and treatment. Because of the spatiotemporal variability of miRNA expression level during different cell cycles, signal amplification strategies that can be activated by external stimuli are required to image miRNAs on demand at desired times and selected locations. Herein, we develop a signal amplification strategy termed as the photoactivated DNA walker based on DNA nanoflares, which enables photocontrollable signal amplification imaging of cancer-related miRNA in single living cells. The developed method is achieved via combining photoactivated nucleic acid displacement reaction with the traditional exonuclease III (EXO III)-assisted DNA walker based on DNA nanoflares. This method is capable of on-demand activation of the DNA walker for dictated signal amplification imaging of cancer-related miRNA in single living cells. The developed method was demonstrated as a proof of concept to achieve photoactivated signal amplification imaging of miRNA-21 in single living HeLa cells via selective two-photon irradiation (λ = 740 nm) of single living HeLa cells by using confocal microscopy equipped with a femtosecond laser.