Naphtho[1,8-ef]isoindole-7,8,10(9H)-trione as novel theranostic agents for photodynamic therapy and multi-subcellular organelles localization.

A series of naphtho[1,8-ef]isoindole-7,8,10(9H)-trione as novel theranostic agents for photodynamic therapy and multi-subcellular organelles localization were designed and synthesized. Most of them possess moderate fluorescence quantum yield and long wavelength absorption simultaneously, these made them possible for dual effects of imaging and therapy. Especially, 7b and 7d exhibited significant light-toxicity but slight dark-toxicity. Confocal fluorescence microscopy experiments demonstrated that 7b can locate and image in special multi-subcellular organelles. All the research results implied that carbonyl-phenalene-2,3-dicarboximides derivatives can be applied as a new series of theranostic agents with the characteristics of photodynamic therapy and multi-subcellular organelles imaging.

Study on anisotropy orientation due to well-ordered fibrous biological microstructures.

Significance: Most biological fibrous tissues have anisotropic optical characteristics, which originate from scattering by their fibrous microstructures and birefringence of biological macromolecules. The orientation-related anisotropic interpretation is of great value in biological tissue characterization and pathological diagnosis. Aim: We focus on intrinsic birefringence and form birefringence in biological tissue samples. By observing and comparing the forward Mueller matrix of typical samples, we can understand the interpretation ability of orientation-related polarization parameters and further distinguish the sources and trends of anisotropy in tissues. Approach: For glass fiber, silk fiber, skeletal muscle, and tendon, we construct a forward measuring device to obtain the Mueller matrix image and calculate the anisotropic parameters related to orientation. The statistical analysis method based on polar coordinates can effectively analyze the difference in anisotropic parameters. Results: For those birefringent fibers, the statistical distribution of fast-axis values derived from Mueller matrix polar decomposition was found to exhibit bimodal characteristics, which is a key point in distinguishing the single-layer birefringent fiber sample from a layered, multioriented fibrous sample. The application conditions and interference factors of anisotropic orientation parameters are analyzed. Based on the parameters extracted from the orientation bimodal distribution, we can evaluate the relative change trend of intrinsic birefringence and form birefringence in anisotropic samples. Conclusions: The cross-vertical bimodal distribution of the fast axis of anisotropic fibers is beneficial to accurately analyze the anisotropic changes in biological tissues. The results imply the potential of anisotropic orientation analysis for applications in pathological diagnosis.

Effect of photobiomodulation on alleviating primary dysmenorrhea caused by PGF2α.

Photobiomodulation (PBM) has attracted widespread attention in suppressing various pain and inflammation. Primary dysmenorrhea (PD) primarily occurs in adolescents and adult females, and the limited effectiveness and side effects of conventional treatments have highlighted the urgent need to develop and identify new adjunct therapeutic strategies. In this work, the results of pain and PGs demonstrated that 850 nm, 630 nm, and 460 nm all exhibited pain inhibition, decreased PGF2α and upregulated PGE2, while 630 nm PBM has better effectiveness. Then to explore the underlying biological mechanisms of red light PBM on PD, we irradiated prostaglandin-F2α induced HUSM cells and found that low-level irradiance can restore intracellular calcium ion, ROS, ATP, and MMP levels to normal levels. And, red light enhanced cell viability and promoted cell proliferation for normal HUSM cells. Therefore, this study proposes that red light PBM may be a promising approach for the future clinical treatment of PD.

Multiple Fluorescences in Situ Hybridization Status in Excreted Urine Improve Diagnostic Efficacy for Upper Urinary Tract Urothelial Carcinomas.

PURPOSE: To evaluate the diagnostic accuracy of single and multiple fluorescence in situ hybridization (FISH) tests for upper urinary tract cancer (UTUC), we analyzed the diagnostic efficacy of FISH in patients with UTUC and the difference between it and the Tumor Node Metastasis (TNM) stage and grade of the tumor. MATERIALS AND METHODS: Patients treated for UTUC at our institution between 2011 and 2021 who had not been previously diagnosed with UTUC were included. Patients were divided into single, two, and multiple (three times or four times) FISH groups based on the number of FISH tests performed on different samples from the same patient, and the diagnostic efficiency of single, two, and multiple FISH tests for muscle-invasive tumors and highgrade tumors were assessed. RESULTS: We included a total of 207 patients with UTUC, and when compared to single FISH, the sensitivity of multiple and double FISH for the diagnosis of UTUC increased from 62% to 76% and 78%, respectively. It went from 67% to 78% and 80% for muscle-invasive UTUC (> = pT2) and from 71% to 79% and 81% for the highest- grade UTUC. CONCLUSION: Multiple FISH improves the diagnostic efficacy of UTUC and helps to differentiate aggressive tumors.

Effects of oxytetracycline on variation in intracellular and extracellular antibiotic resistance genes during swine manure composting.

This research aimed to investigate the alterations in extracellular (eARGs) and intracellular (iARGs) antibiotic resistance genes in response to oxytetracycline (OTC), and unravel the dissemination mechanism of ARGs during composting. The findings revealed both low (L-OTC) and high contents (H-OTC) of OTC significantly enhanced absolute abundance (AA) of iARGs (p < 0.05), compared to CK (no OTC). Composting proved to be a proficient strategy for removing eARGs, while AA of eARGs was significantly enhanced in H-OTC (p < 0.05). OTC resulted in an increase in AA of mobile genetic elements (MGEs), ATP levels, antioxidant and DNA repair enzymes in bacteria in compost product. Structural equation model further demonstrated that OTC promoted bacterial DNA repair and antioxidant enzyme activities, altered bacterial community and enhanced MGEs abundance, thereby facilitating iARGs dissemination. This study highlights OTC can increase eARGs and iARGs abundance, underscoring the need for appropriate countermeasures to mitigate potential hazards.

Historical Misdiagnosis of Recurrent Solitary Fibroma Tumor of the Prostate: A Cases Report and Current Evidence.

BACKGROUND: Solitary fibrous tumors (SFTs) manifest in various anatomical locations but are seldom encountered in the prostate. Despite their rare occurrence in this region, SFTs demonstrate a marked propensity for recurrence. This study elucidates a case of recurrent prostate SFT, previously misdiagnosed, and delineates the salient features and diagnostic criteria pertaining for SFTs. METHODS: Through a meticulous analysis of the patient's antecedent medical records and corroborative diagnostic evaluations, we hypothesized that the presenting pathology was indicative of a prostate SFT. In order to substantiate this supposition, we re-examined archival pathological specimens from the patient. The ensuing pathological assessment validated our conjecture. To address the recurrence, we conducted an open surgical procedure to excise the tumor. Subsequent postoperative pathological evaluations further corroborated the diagnosis of prostate SFT. RESULTS: Upon re-evaluation of the patient's earlier pathological specimens, we discerned that what had been previously classified as a "seminal vesicle tumor" was, in fact, a prostate SFT. During the surgical intervention, it was observed that the prostatic tumor had invaded the bladder, yet there was no seminal vesicle involvement. The tumor dimensions were approximately 7 × 5 × 4 cm, and the margin between the tumor and the surgical resection edge was less than 0.1 cm. The postoperative histological analysis confirmed the diagnosis of recurrent prostate SFT, substantiating our designation of the patient's condition as such. A year-long follow-up revealed no conspicuous signs of tumor recurrence. CONCLUSIONS: Therapeutic intervention for prostate SFT is predominantly surgical. However, given the tumor's marked predisposition for recurrence, the specific mechanisms underlying its etiology and pathogenesis remain enigmatic. Hence, a comprehensive understanding of its pathogenic and recurrent characteristics, coupled with regular postoperative surveillance, is imperative for efficacious treatment and prevention of prostate SFT.

Blue light photobiomodulation induced apoptosis by increasing ROS level and regulating SOCS3 and PTEN/PI3K/AKT pathway in osteosarcoma cells.

Blue light photobiomodulation (PBM) has attracted great attention in diminishing proliferation and inducing death of cancer cells recently. Osteosarcoma (OS) primarily occurring in children and adolescents, the limitations of drug resistance and limb salvage make it urgent to develop and identify new adjuvant therapeutic strategies. In this work, we attempted to research the anticancer effects and biological mechanisms of blue light PBM in human OS MG63 cells. The effects of various blue light parameters on MG63 cells indicated that suppressed cell proliferation and cell migration, induced cell apoptosis which are experimentally assessed using multiple assays including CCK, LDH, wound healing assay and Hoechst staining. Concurrently, the increases of ROS level and the inhibition of PI3K and AKT expression were identified under high-dose blue light PBM in MG63 cells. Meanwhile, SOCS3 is a major inducible anti-tumor molecule, we also found that blue light LED substantially promoted its expression. Thus, this study proposed that bule light PBM may be a hopeful therapeutic approach in OS clinical treatment in the future.

Historical Misdiagnosis of Recurrent Solitary Fibroma Tumor of the Prostate: A Cases Report and Current Evidence

Background: Solitary fibrous tumors (SFTs) manifest in various anatomical locations but are seldom encountered in the prostate. Despite their rare occurrence in this region, SFTs demonstrate a marked propensity for recurrence. This study elucidates a case of recurrent prostate SFT, previously misdiagnosed, and delineates the salient features and diagnostic criteria pertaining for SFTs. Methods: Through a meticulous analysis of the patient’s antecedent medical records and corroborative diagnostic evaluations, we hypothesized that the presenting pathology was indicative of a prostate SFT. In order to substantiate this supposition, we re-examined archival pathological specimens from the patient. The ensuing pathological assessment validated our conjecture. To address the recurrence, we conducted an open surgical procedure to excise the tumor. Subsequent postoperative pathological evaluations further corroborated the diagnosis of prostate SFT. Results: Upon re-evaluation of the patient’s earlier pathological specimens, we discerned that what had been previously classified as a “seminal vesicle tumor” was, in fact, a prostate SFT. During the surgical intervention, it was observed that the prostatic tumor had invaded the bladder, yet there was no seminal vesicle involvement. The tumor dimensions were approximately 7 × 5 × 4 cm, and the margin between the tumor and the surgical resection edge was less than 0.1 cm. The postoperative histological analysis confirmed the diagnosis of recurrent prostate SFT, substantiating our designation of the patient’s condition as such. A year-long follow-up revealed no conspicuous signs of tumor recurrence. Conclusions: Therapeutic intervention for prostate SFT is predominantly surgical. However, given the tumor’s marked predisposition for recurrence, the specific mechanisms underlying its etiology and pathogenesis remain enigmatic (AU)

Designing nanohesives for rapid, universal, and robust hydrogel adhesion.

Nanoparticles-based glues have recently been shown with substantial potential for hydrogel adhesion. Nevertheless, the transformative advance in hydrogel-based application places great challenges on the rapidity, robustness, and universality of achieving hydrogel adhesion, which are rarely accommodated by existing nanoparticles-based glues. Herein, we design a type of nanohesives based on the modulation of hydrogel mechanics and the surface chemical activation of nanoparticles. The nanohesives can form robust hydrogel adhesion in seconds, to the surface of arbitrary engineering solids and biological tissues without any surface pre-treatments. A representative application of hydrogel machine demonstrates the tough and compliant adhesion between dynamic tissues and sensors via nanohesives, guaranteeing accurate and stable blood flow monitoring in vivo. Combined with their biocompatibility and inherent antimicrobial properties, the nanohesives provide a promising strategy in the field of hydrogel based engineering.

Simultaneous passivation of heavy metals and removal of antibiotic resistance genes by calcium peroxide addition during sewage sludge composting.

This research evaluated the effects of calcium peroxide (CP) at 0% (CK, w/w), 5% (T1, w/w), and 10% (T2, w/w), on heavy metals (HMs) mobility and prevalence of antibiotic resistance genes (ARGs) during sludge composting. T1 and T2 significantly reduced (p < 0.05) the mobility of Cu (29.34%, and 32.94%, respectively), Ni (24.07%, and 31.48%, respectively) and Zn (33.28%, and 54.11%, respectively) compared to CK after the composting. CP addition resulted in a decrease in mobile genetic elements (MGEs) and ARGs during composting. Together with structural equation model and random forest analysis depicted MGEs had a primary association with total ARGs variations during composting. Microbial analysis indicated CP downregulated the expression of the genes associated with two-component and type IV secretion system, thus reducing the prevalence of ARGs. This study demonstrates that application of CP is a feasible strategy to mitigate both ARGs and HMs hazards during composting.

STIL Promotes Tumorigenesis of Bladder Cancer by Activating PI3K/AKT/mTOR Signaling Pathway and Targeting C-Myc.

SCL/TAL1 interrupting locus (STIL) regulates centriole replication and causes chromosome instability, which is closely related to malignant tumors. The purpose of our study was to investigate the role of STIL in bladder cancer (BC) tumorigenesis for the first time. The public database indicated that STIL is highly expressed and correlated with the cell cycle in BC. Immunohistochemistry staining showed that STIL expression is significantly elevated in BC tissues compared with paracancer tissues. CRISPR-Cas9 gene editing technology was used to induce BC cells to express STIL-specific sgRNA, revealing a significantly delayed growth rate in STIL knockout BC cells. Moreover, cell cycle arrest in the G0/G1 phase was triggered by decreasing STIL, which led to delayed BC cell growth in vitro and in vivo. Mechanically, STIL knockout inhibited the PI3K/AKT/mTOR pathway and down-regulated the expression of c-myc. Furthermore, SC79 (AKT activating agent) partially reversed the inhibitory effects of STIL knockout on the proliferation and migration of BC cells. In conclusion, STIL enhanced the PI3K/AKT/mTOR pathway, resulting in increased expression of c-myc, ultimately promoting BC occurrence and progression. These results indicate that STIL might be a potential target for BC patients.

Progress of phototherapy for osteosarcoma and application prospect of blue light photobiomodulation therapy.

Osteosarcoma (OS) is the most common primary malignant bone tumor that mainly affects the pediatric and adolescent population; limb salvage treatment has become one of the most concerned and expected outcomes of OS patients recently. Phototherapy (PT), as a novel, non-invasive, and efficient antitumor therapeutic approach including photodynamic therapy (PDT), photothermal therapy (PTT), and photobiomodulation therapy (PBMT), has been widely applied in superficial skin tumor research and clinical treatment. OS is the typical deep tumor, and its phototherapy research faces great limitations and challenges. Surprisingly, pulse mode LED light can effectively improve tissue penetration and reduce skin damage caused by high light intensity and has great application potential in deep tumor research. In this review, we discussed the research progress and related molecular mechanisms of phototherapy in the treatment of OS, mainly summarized the status quo of blue light PBMT in the scientific research and clinical applications of tumor treatment, and outlooked the application prospect of pulsed blue LED light in the treatment of OS, so as to further improve clinical survival rate and prognosis of OS treatment and explore corresponding cellular mechanisms.

Effect of calcium peroxide dosage on organic matter degradation, humification during sewage sludge composting and application as amendment for Cu (II)-polluted soils.

In this research, it was the first time to investigate the effect of two dosages (5% (T1) and 10% (T2), w/w) of calcium peroxide (CP) on organic matter degradation, humification during sewage sludge composting. Additionally, the complexation of Cu to humic substance (HS) derived from CP-compost compared to no CP addition-compost (CK) was also studied. Results showed that compared to CK, T1 and T2 significantly enhanced organic matter degradation and promoted the formation of HS. Two-dimensional correlation Fourier transform infrared spectroscopy (2D-FTIR-COS) and Parallel factor (PARAFAC) analysis revealed that the addition of CP accelerated the synthesis of HS with high aromatization degree and molecular weight than those in CK, owing to the oxidation of small molecules to form carboxyl. The stability constant (log KM) of Cu with CP-derived HS (log KM = 4.22-5.13) indicated a greater complexation ability than CK-derived HS (log KM = 4.05-4.45), due to the faster response of polysaccharides binding to Cu (II) and the higher humification degree of CP-derived HS. This study revealed the potential mechanisms of CP addition on the synthesis of HS and utilization of CP-compost product might provide an effective way to remedy Cu (II)-contaminated soils.

NCAPG promotes tumorigenesis of bladder cancer through NF-κB signaling pathway.

The non-SMC condensin I complex subunit G (NCAPG) is a subunit of the condensin complex, many studies have shown that NCAPG is aberrantly expressed in different tumors and closely associated with poor prognosis, but its role in bladder cancer is unclear. In this paper, we found that NCAPG expression was upregulated in bladder cancer in tumor-related databases, and further verified the expression of NCAPG in bladder cancer tissues as well as bladder cancer cell lines by tissue microarray, qPCR, and WB. Next, we explored the changes in bladder cancer cell proliferation as well as migration after NCAPG knockdown by cell growth curve, colony formation, soft agar assay, and xenograft model. Finally, we examined the changes in downstream signaling pathways after NCAPG knockdown using RNA-Seq, and we found that the NF-κB signaling pathway was inhibited with NCAPG gene knockdown, which was verified by luciferase reporter assay as well as WB. In conclusion, our results illustrate that NCAPG knockdown can inhibit the proliferation of bladder cancer cells through the NF-κB signaling pathway. This finding demonstrates that NCAPG could be a potential target for the treatment of bladder cancer.

Response of antibiotic resistance to the co-exposure of sulfamethoxazole and copper during swine manure composting.

Heavy metals driven co-selection of antibiotic resistance in soil and water bodies has been widely concerned, but the response of antibiotic resistance to co-existence of antibiotics and heavy metals in composting system is still unknown. Commonly used sulfamethoxazole and copper were individually and jointly added into four reactors to explore their effects on antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), heavy metal resistance genes (MRGs) and bacterial community structure. The abundance of total ARGs and MGEs were notably decreased by 68.64%-84.95% and 91.27-97.38%, respectively, after the composting. Individual addition of sulfamethoxazole, individual addition of copper, simultaneously addition of sulfamethoxazole and copper increased the abundance of ARGs and MGEs throughout the composting period. Co-exposure of sulfamethoxazole and copper elevated the total abundance of ARGs by 1.17-1.51 times by the end of the composting compared to individual addition of sulfamethoxazole or copper. Network analysis indicated that the shifts in potential host bacteria determined the ARGs variation. Additionally, MGEs and MRGs had significant effects on ARGs, revealing that horizontal gene transfer and heavy metals induced co-resistance could promote ARGs dissemination.

Microbial community competition rather than high-temperature predominates ARGs elimination in swine manure composting.

Aerobic composting is commonly used in pig manure treatment, however, antibiotic resistance genes (ARGs) and their unclear transformation during composting process make the treated manure land using risky. The effects of enhanced thermophilic phase strategy (external heating (HTC) and thermophiles inoculation (MC)) on ARGs removal and the underlying mechanisms were investigated during swine manure composting. HTC increased the total relative abundance (RA) of ARGs by 32.38%, and MC decreased by 21.50% compared to CK by the end of the composting. Mantel test indicated that it was not temperature (P > 0.05), but environmental parameters (pH, Electric Conductivity (EC), etc.) and metabolic products (nitrogen forms) significantly affected the ARGs profile. Partial least-squares path modeling (PLS-PM) suggested that microbial community structure (bacterial abundance and diversities) was the main factor for ARGs evolution. Co-occurrence analysis revealed that HTC could promote the propagation of ARG hosts in later stage of the composting because the strong selection of thermophiles resulted in ecological niches vacancy, and MC enhanced the competition between hosts and nonhosts for ecological niches by increasing thermophiles diversities. These results suggested that competitive inhibition to potential ARGs hosts could be a helpful strategy in ARGs threaten elimination during composting.

Effects of H3PO4 modified biochar on heavy metal mobility and resistance genes removal during swine manure composting.

In this research, static composting treatments of swine manure with forced ventilation were conducted to study the effects of biochar (BC) and H3PO4 modified biochar (BP) addition on heavy metals (HMs) stabilization, profiles of antibiotic resistance genes (ARGs), heavy metals resistance genes (MRGs) and bacterial communities during swine manure composting. After 42 days of the composting, compared to control (CK), BC and BP decreased the concentration of diethylenetriamine pentaacetic acid extractable Cu and Zn by 12.04%, 15.15% and 26.91%, 36.50%, respectively. Furthermore, BC and BP treatments reduced the total abundances of nine ARGs by 4.02% and 66.21%, and five MRGs by 53.66% and 58.81%, compared to CK in the compost product. Network analysis and square structural equation model analysis revealed that the decrease of ARGs and MRGs in BP treatment was related tothe change in bacterial community during the composting, rather than differences in co-selection pressure.

A fully integrated biomimetic microfluidic device for evaluation of sperm response to thermotaxis and chemotaxis.

In recent decades, humans have faced greater challenges in reproduction. Assisted reproductive technology is the most prominent approach for addressing this problem. Current clinical screening methods simply consider the motility or morphology of the sperm. However, as the spermatozoa need to navigate over a long distance in the female reproductive tract and survive the natural screening processes therein, these methods are imperfect. Many approaches have been undertaken to study the chemotaxis and thermotaxis navigation behavior of spermatozoa, but few of these have involved integrated screening that considers motility, chemotaxis, and thermotaxis based on the biological environment of the human body. Current routine sperm evaluation techniques are inadequate and fail to simultaneously provide conclusive evidence for the thermotactic and chemotactic characteristics of sperm. Thus, such screening of functional spermatozoa will be an advancement in assisted reproduction. In this study, we developed a fully integrated biomimetic microfluidic system for screening sperm for their characteristics when exposed to temperature and chemical gradients. Based on our results, we showed that spermatozoa were attracted by temperature and chemical gradients in the physiological range. Moreover, we ascertained a suitable temperature gradient range for thermotaxis and statistically proved that the thermotactic and chemotactic responses are not linked. Here, we report the first quantitative study of functional sperm during thermotaxis and chemotaxis, and our analysis of the difference in motility caused by different conditions. More broadly, we foresee the clinical application of these biologically motivated parameters and characteristics in assisted reproduction in humans.

Mechanism concerning the occurrence and removal of antibiotic resistance genes in composting product with ozone post-treatment.

The soil application of composting product will probably cause the spread of antibiotic resistance genes (ARGs) to environment, thereby it is crucial to remove ARGs in composting product. Ozone was adopted for the first time as a post-treatment method to remove the ARGs in composting product in this study. Ozone treatment significantly removed the total ARGs and mobile genetic elements (MGEs) once ozonation process finished. After 10-day storage stage, although the amount of total intracellular ARGs and MGEs increased, the total extracellular ARGs and MGEs decreased in the ozone-treated compost product. Correlation analysis revealed that the reduction in intracellular 16S rRNA contributed to intracellular tetQ and tetW removal, while the variations of other ARGs after ozonation related to MGEs abundance. Network analysis suggested that the reduction of potential host bacteria, as well as the decline in NH4+-N and TOC after the ozonation, contributed to the intracellular ARGs removal.

Effects of lime amendment on the organic substances changes, antibiotics removal, and heavy metals speciation transformation during swine manure composting.

Aerobic composting has been used for a long time for bioconversion of manure wastes, however, its application has been limited due to slow transition of organic matters and influence of heavy metals and antibiotics residues. Compost with lime addition can speed up the composting process, while its effects on the evolution of organic matters, heavy metals and antibiotics need to be further investigated. In this research, the effects of lime amendment on organic substances changes was assessed by the spectroscopic characteristics. Besides, chlortetracycline (CTC) removal and Cu, Zn chemical speciation transformation were also evaluated. Results showed that the humic acid-like substances region of fluorescence regional integration (FRI-EEM) increased from 20.5% to 40.9% and 20.6%-32.6%, respectively, in lime addition treatment and control after 15 days of composting, indicating that the addition of lime remarkably improved the transition of organic matter and accelerated the maturity process. Besides, 94.04% of CTC in the manure was removed when lime was added, higher than 86.10% in the control group. The transformation of zinc from exchangeable and reducible into oxidizable and residual fractions was improved while the transformation of copper was affected slightly. Therefore, lime is a suitable amendment material for manure composting, which can accelerate the transition of organic matters due to the regulation of composting pH, as well as eliminate harmful CTC and bioavailable heavy metal, thus promoting the further utilizing of organic substance.