Ultrasmall Bi/Cu Coordination Polymer Combined with Glucose Oxidase for Tumor Enhanced Chemodynamic Therapy by Starvation and Photothermal Treatment.

Multi-modal combination therapy for tumor is expected to have superior therapeutic effect compared with monotherapy. In this study, a super-small bismuth/copper-gallic acid coordination polymer nanoparticle (BCN) protected by polyvinylpyrrolidone is designed, which is co-encapsulated with glucose oxidase (GOX) by phospholipid to obtain nanoprobe BCGN@L. It shows that BCN has an average size of 1.8 ± 0.7 nm, and photothermal conversion of BCGN@L is 31.35% for photothermal imaging and photothermal therapy (PTT). During the treatment process of 4T1 tumor-bearing nude mice, GOX catalyzes glucose in the tumor to generate gluconic acid and hydrogen peroxide (H2 O2 ), which reacts with copper ions (Cu2+ ) to produce toxic hydroxyl radicals (•OH) for chemodynamic therapy (CDT) and new fresh oxygen (O2 ) to supply to GOX for further catalysis, preventing tumor hypoxia. These reactions increase glucose depletion for starvation therapy , decrease heat shock protein expression, and enhance tumor sensitivity to low-temperature PTT. The in vitro and in vivo results demonstrate that the combination of CDT with other treatments produces excellent tumor growth inhibition. Blood biochemistry and histology analysis suggests that the nanoprobe has negligible toxicity. All the positive results reveal that the nanoprobe can be a promising approach for incorporation into multi-modal anticancer therapy.

Identification and fungicide sensitivity of Microdochiumchrysopogonis (Ascomycota, Amphisphaeriaceae), a new species causing tar spot of Chrysopogonzizanioides in southern China.

Vetiver grass (Chrysopogonzizanioides) has received extensive attention in recent years due to its diverse applications in soil and water conservation, heavy metal remediation, as well as essential oil and phenolic acids extraction. In 2019, the emergence of tar spot disease on C.zizanioides was documented in Zhanjiang, Guangdong Province, China. Initially, the disease manifested as black ascomata embedded within leaf tissue, either scattered or clustered on leaf surfaces. Subsequently, these ascomata became surrounded by fisheye lesions, characterised by brown, elliptical, necrotic haloes, which eventually coalesced, resulting in leaf withering. Koch's postulates demonstrated that the fungus isolated from these lesions was the causal agent. Microscopic examination showed that the pathogen morphologically belonged to Microdochium. The phylogenetic tree inferred from the combined ITS, LSU, tub2 and rpb2 sequences revealed the three isolates including GDMCC 3.683, LNU-196 and LNU-197 to be a novel species of Microdochium. Combining the results of phylogenetic, pathogenicity and morphological analyses, we propose a new species named M.chrysopogonis as the causal agent of C.zizanioides in southern China. The optimum growth temperature for M.chrysopogonis was determined to be 30 °C. The in vitro fungicide sensitivity of M.chrysopogonis was determined using a mycelial growth assay. Four demethylation-inhibiting (DMI) fungicides, including difenoconazole, flusilazole, propiconazole and tebuconazole and one methyl benzimidazole carbamate (MBC) fungicide, carbendazim, were effective against M.chrysopogonis, with mean 50% effective concentration (EC50) values of 0.077, 0.011, 0.004, 0.024 and 0.007 µg/ml, respectively. These findings provide essential references for the precise diagnosis and effective management of M.chrysopogonis.

Impact of Allee and fear effects in a fractional order prey-predator system with group defense and prey refuge.

This paper presents a novel fractional-order model of a prey-predator system that incorporates group defense and prey refuge mechanisms, along with Allee and fear effects. First, we examine the existence, uniqueness, non-negativity, and boundedness of the solution of the system. Second, a comprehensive analysis is conducted on the existence, stability, and coexistence of equilibrium states in the system, which are crucial for comprehending prey-predator system behavior. Our investigation reveals that the coexistence equilibrium undergoes a Hopf bifurcation under five key parameters. Specifically, an increased threshold for the transition between group and individual behavior, influenced by different strengths of the Allee effect, enhances the stability of both populations. This discovery sheds light on the role of group effects in shaping prey-predator interactions and ecosystem stability. Third, system discretization is employed to explore the impact of step size on stimulating stability and to investigate the Neimark-Sacker bifurcation, providing a more comprehensive understanding of system behavior. The role of step size as a constraint on stability is examined, revealing the system's progression from stability to chaos. Consequently, our results offer a more flexible mechanism for adjusting the stability and dynamics of the two species. Finally, numerical simulations are utilized to validate the reasonableness of the research findings.

The epigenetic regulatory mechanism of PIWI/piRNAs in human cancers.

PIWI proteins have a strong correlation with PIWI-interacting RNAs (piRNAs), which are significant in development and reproduction of organisms. Recently, emerging evidences have indicated that apart from the reproductive function, PIWI/piRNAs with abnormal expression, also involve greatly in varieties of human cancers. Moreover, human PIWI proteins are usually expressed only in germ cells and hardly in somatic cells, so the abnormal expression of PIWI proteins in different types of cancer offer a promising opportunity for precision medicine. In this review, we discussed current researches about the biogenesis of piRNA, its epigenetic regulatory mechanisms in human cancers, such as N6-methyladenosine (m6A) methylation, histone modifications, DNA methylation and RNA interference, providing novel insights into the markers for clinical diagnosis, treatment and prognosis in human cancers.

In situ preparation of molybdenum-dioxide-incorporated carbonized silk fiber and its application in supercapacitors.

A previous study found that the capacitive behavior of nanoparticles fed to the silkworm can be delivered to carbonized silk fibers, which can be used to fabricate electrodes for the construction of flexible supercapacitors. However, the tendency of nanoparticles to aggregate decreases the quantity of nanoparticles that enter the silk and therefore reduces the capacitance performance of the prepared carbonized silk. Here, we sprayed ammonium molybdate tetrahydrate (AMT) on the surface of mulberry leaves used for feeding silkworms and investigated the effect of feeding AMT on the growth of silkworms and the properties of spun silk. The precursor incorporated into the silk was converted into scattered MoO2 NPs, which were embedded within the carbonized silk fiber (CSF) via carbothermal reduction. The specific capacitance of CSF obtained from silkworms fed with an aqueous solution of AMT-treated mulberry leaves reached up to 298 F/g at 0.2 g/A, which is much higher than that of the control group (102 F/g). Since AMT is highly water-soluble, and its concentration can be easily modulated, we believe that the proposed strategy is feasible for the large-scale fabrication of CSF with enhanced capacitive performance.

Microbiota analysis with next-generation 16S rDNA gene sequencing in recurrent common bile duct stones.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is the main remedy for gallstones, but the postoperative recurrence rate is high. Recent research has indicated that the biliary microbiome takes part in the pathogenesis of cholelithiasis. However, it is not yet known whether biliary microbiome dysbiosis is relevant to recurrent cholelithiasis. Methods: Thus, we investigated the bacterial communities of the biliary microbiomes of patients with recurrent common bile duct (CBD) stones and analyzed the relationship between recurrent CBD stones and biliary microbiota. The bile specimens of 5 patients with recurrent CBD stones (FF) and 45 patients with primary CBD stones (YF) were collected during the ERCP process. The microbiota was analyzed using 16S ribosomal DNA (rDNA) high-throughput sequencing. We also identified the link between recurrent CBD stones and biliary microbiota. Results: Our results showed that at the phylum level, proteobacteria and firmicutes were the main two genera groups, and proteobacteria was high in FF patients. Additionally, synergistetes were high, but Bacteroidetes and actinobacteria were low in FF patients. The microbiomes in the bile of the YF patients were more evenly distributed than those in the bile of the FF patients. We also discovered that FF patients had decreased microbial bile diversity. At the genus level, klebsiella dominated in the FF patients, while Escherichia-shigella dominated in the YF patients. Additionally, klebsiella was higher in the FF patients than the YF patients. Conclusions: The observed differences in the genera between the recurrent CBD stone FF patients and the YF patients provide novel insights into the link between biliary microbiota changes and recurrent CBD stones.

Microbiologic risk factors of recurrent choledocholithiasis post-endoscopic sphincterotomy.

BACKGROUND: Choledocholithiasis is a severe disorder that affects a significant portion of the world's population. Treatment using endoscopic sphincterotomy (EST) has become widespread; however, recurrence post-EST is relatively common. The bile microbiome has a profound influence on the recurrence of choledocholithiasis in patients after EST; however, the key pathogens and their functions in the biliary tract remain unclear. AIM: To investigate the biliary microbial characteristics of patients with recurrent choledocholithiasis post-EST, using next-generation sequencing. METHODS: This cohort study included 43 patients, who presented with choledocholithiasis at the Guangdong Second Provincial General Hospital between May and June 2020. The patients had undergone EST or endoscopic papillary balloon dilation and were followed up for over a year. They were divided into either the stable or recurrent groups. We collected bile samples and extracted microbial DNA for analysis through next-generation sequencing. Resulting sequences were analyzed for core microbiome and statistical differences between the diagnosis groups; they were examined using the Kyoto Encyclopedia of Genes and Genomes pathway hierarchy level using analysis of variance. Correlation between the key genera and metabolic pathways in bile, were analyzed using Pearson's correlation test. RESULTS: The results revealed distinct clustering of biliary microbiota in recurrent choledocholithiasis. Higher relative abundances (RAs) of Fusobacterium and Neisseria (56.61% ± 14.81% vs 3.47% ± 1.10%, 8.95% ± 3.42% vs 0.69% ± 0.32%, respectively) and the absence of Lactobacillus were observed in the bile of patients with recurrent disease, compared to that in stable patients. Construction of a microbiological co-occurrence network revealed a mutual relationship among Fusobacterium, Neisseria, and Leptotrichia, and an antagonistic relationship among Lactobacillales, Fusobacteriales, and Clostridiales. Functional prediction of biliary microbiome revealed that the loss of transcription and metabolic abilities may lead to recurrent choledocholithiasis. Furthermore, the prediction model based on the RA of Lactobacillales in the bile was effective in identifying the risk of recurrent choledocholithiasis (P = 0.03). CONCLUSION: We demonstrated differences in the bile microbiome of patients with recurrent choledocholithiasis compared to that in patients with stable disease, thereby adding to the current knowledge on its microbiologic etiology.

Whole-Process Emergency Training of Personal Protective Equipment Helps Healthcare Workers Against COVID-19: Design and Effect.

OBJECTIVE: To develop an emergency training program of personal protective equipment (PPE) for general healthcare workers (HCWs) who may be under the threat of Corona Virus Disease 2019 (COVID-19) and evaluate the effect of the program. METHODS: A three-stage training program was designed. The complete clinical workflow together with infectious disease ward was simulated. To verify the effect of the program, an experimental training with pre- and post-test was conducted before large-scale training. RESULTS: Post-test scores were significantly improved when compared with the pre-test scores. Among all PPE, N95 respirator and protective coverall needed training most. Meanwhile, "proficiency level" and "mutual check & help" also needed to be strengthened as independent scoring points. CONCLUSION: This training program significantly improved the performances of participants. It may therefore be applied for general HCWs on a larger scale.

Astragalus Polysaccharide Promotes Adriamycin-Induced Apoptosis in Gastric Cancer Cells.

PURPOSE: Astragalus polysaccharide (APS), a common Chinese herbal compound extracted from Astragalus membranaceus, has been proposed to increase the tumour response of and stabilize chemotherapy drugs while reducing their toxicity. Here, we examined the effects of APS on apoptosis in gastric cancer (GC) cells in the presence or absence of adriamycin (0.1 µg/mL). METHODS: GC cells cultured in the presence or absence of adriamycin (0.1 µg/mL) were administered APS (50-200 µg/mL) for 24-72 h and subjected to an MTT assay to examine cell viability. Active caspase-3 expression and DNA fragmentation were assessed to evaluate apoptosis, and real-time PCR was used to analyse the expression levels of multidrug resistance (MDR1) genes and tumour suppressor genes. Western blot analysis was applied to detect cleaved caspase-3 and phosphorylated AMPK (p-AMPK). RESULTS: Cellular viability was profoundly reduced by APS, and GC cell apoptosis was strongly increased by APS in a time- and dose-dependent manner; these changes may be linked to an increase in p-AMPK levels because the AMPK inhibitor compound C blocked the effects of APS. Similarly, adriamycin-induced decreases in cellular viability and apoptosis of GC cells were enhanced by APS administration. The expression of tumour suppressor genes (SEMA3F, P21WAF1/CIP1, FBXW7), but not of MDR1, was increased by APS compared to the control, and p-AMPK levels were lower in adriamycin-resistant GC cells than in either adriamycin-sensitive GC cells or an immortalized human gastric epithelial cell line. CONCLUSION: APS induces apoptosis independently and strengthens the proapoptotic effect of adriamycin on GC cells, suggesting that APS may act as a chemotherapeutic sensitizer.

Adipose tissue location and contribution to postinjury hypercoagulability.

OBJECTIVES: Obesity is associated with a hypercoagulable state at baseline and following injury. The anatomic location of adipose deposition may influence the type of thrombotic event, with visceral adipose tissue (VAT) associated with arterial thrombosis and subcutaneous adipose tissue (SAT) predisposing to venous thrombosis. We sought to determine whether adipose tissue amount and location correlated with measures of coagulation. METHODS: All adult Level I trauma activations at our institution between January 2013 and August 2014 who underwent admission abdominal computed tomography scan and had admission rotational thromboelastometry measurements were included. Patients were excluded for history of anticoagulant use and known coagulopathy/hypercoagulable state. Admission computed tomography was used to obtain cross-sectional VAT and SAT areas at the umbilicus utilizing a novel software system; VAT and SAT measurements were associated with markers of coagulation utilizing Spearman correlation and stepwise linear regression with significance set at p < 0.05. RESULTS: Two hundred forty-two patients met inclusion and exclusion criteria. Sixty-nine percent of patients sustained blunt injury, 79% were male, mean age was 40 years, 25% were obese or morbidly obese, and mean Injury Severity Scale score was 17. Seventeen percent of patients had acute deep venous thrombosis or pulmonary embolism during hospitalization. Neither SAT nor VAT correlated with prothrombin time, international normalized ratio, or partial thromboplastin time. Subcutaneous adipose tissue correlated positively with platelet count. Visceral adipose tissue and SAT correlated negatively with clot formation time and positively with TEM fibrinogen, α angle, maximum clot firmness, and lysis at 30 minutes; stronger correlations and greater significance were seen between SAT and these measures except for lysis at 30 minutes. Stepwise linear regression confirmed significant relationships between SAT and clot formation time, AA, and maximum clot firmness; VAT showed a significant relationship with TEM fibrinogen. CONCLUSIONS: Increased adipose tissue correlates with relative hypercoagulability following trauma. Subcutaneous adipose tissue shows a stronger relationship with functional measures of coagulation, suggesting that SAT may be associated with hemorrhage resistance and hypercoagulability after injury. LEVEL OF EVIDENCE: Prognostic study, level IV.

[The studies for activating and inhibitory receptors on natural killer cells in HIV/HCV co-infected patients].

OBJECTIVE: To investigate the characteristics of inhibitory and activating receptor expressions on natural killer (NK) cells in HIV/HCV co-infected patients. METHODS: Numbers, frequencies and expressions of activating and inhibitory receptors of NK cells were measured with flow cytometry (FCS) from HIV/HCV co-infected group (n = 24), HCV mono-infected group (n = 34), HIV mono-infected group (n = 21) and healthy control group (HC, n = 20), then analysis and compare were performed among those groups. RESULTS: The NK cell absolute counts in HIV/HCV group were significantly lower than those in other three groups. The NKP30 and NKP46 frequencies on NK cells in HIV/HCV, HIV and HCV groups were all significantly lower than those in HC group, but there were no significant differences of NKP30 among former three groups; and NKP46 frequencies in HIV/HCV and HIV groups were lower than those in HCV group, but there were no significant differences between former two groups. The NKG2A frequencies in HIV/HCV and HCV groups were all higher than those in HIV and HC groups significantly, but the NKG2A frequencies in HIV group were lower than those in HC group; There were no significant differences of NKG2D, CD158a and CD158b among those four groups. CONCLUSION: NK cell numbers and expressions of activiting receptors on NK cells obviously decreased in HIV/HCV co-infected patients, but some inhibitory receptors expressions increased, even higher than those of HIV mono-infected patients. NK cells impairments in HIV/HCV co-infection is more severe than HIV or HCV mono-infection.

Construction of a replacement vector to disrupt pksCT gene for the mycotoxin citrinin biosynthesis in Monascus aurantiacus and maintain food red pigment production.

More and more people pay attention to citrinin produced by Monascus, which has nephrotoxic activity in mammals. It was reported that pksCT gene is responsible for citrinin biosynthesis in Monascus purpureus. In this paper, two DNA fragments in both ends of pksCT were amplified by genomic PCR from fourteen Monascus spp. strains. The PCR products were gained from all of the strains. It is suggested that pksCT gene was highly conserved in different citrinin-producing Monascus strains. A pksCT-replacement vector (pHD106) was constructed to disrupt pksCT with a hygromycin resistance gene as the selection marker, and was transformed into M. aurantiacus Li AS3.4384. Three transformants (M. aurantiacus PHDS18, PHDS26, PHDS31) were selected from transformant selective plates. The targeting fragment D was gained by genomic PCR from PHDS18 and PHDS26 except PHDS31. The expressing citrinin capacities of PHDS26 was decreased by about 98%, while PHDS18 was reserved the high capacity of producing citrinin, after 10 days of growth on YM medium. The results indicated that PHDS26 is a pksCT-disrupted strain. There are maybe other genes besides pksCT responsible for citrinin biosynthesis in M. aurantiacus. It is the effective way to solve the problem of citrinin in M. aurantiacus products by constructing replacement vectors to disrupt the genes responsible for citrinin biosynthesis to reduce the capacity of expressing citrinin.