Greatly isolated heterogeneous circulating tumor cells using hybrid engineered cell membrane-camouflaged magnetic nanoparticles.

BACKGROUND: Circulating tumor cells (CTCs) are considered as a useful biomarker for early cancer diagnosis, which play a crucial role in metastatic process. Unfortunately, the tumor heterogeneity and extremely rare occurrence rate of CTCs among billions of interfering leukocytes seriously hamper the sensitivity and purity of CTCs isolation. METHODS: To address these, we firstly used microfluidic chips to detect the broad-spectrum of triple target combination biomarkers in CTCs of 10 types of cancer patients, including EpCAM, EGFR and Her2. Then, we constructed hybrid engineered cell membrane-camouflaged magnetic nanoparticles (HE-CM-MNs) for efficient capture of heterogeneous CTCs with high-purity, which was enabled by inheriting the recognition ability of HE-CM for various CTCs and reducing homologous cell interaction with leukocytes. Compared with single E-CM-MNs, HE-CM-MNs showed a significant improvement in the capture efficiency for a cell mixture, with an efficiency of 90%. And the capture efficiency of HE-CM-MNs toward 12 subpopulations of tumor cells was ranged from 70 to 85%. Furthermore, by using HE-CM-MNs, we successfully isolated heterogeneous CTCs with high purity from clinical blood samples. Finally, the captured CTCs by HE-CM-MNs could be used for gene mutation analysis. CONCLUSIONS: This study demonstrated the promising potential of HE-CM-MNs for heterogeneous CTCs detection and downstream analysis.

CircVDAC3 sequesters microRNA-592 and elevates EIF4E3 expression to inhibit the progression of gastric cancer.

BACKGROUND: Accumulating evidence has shown that circular RNAs (circRNAs) are involved in gastric cancer (GC) tumorigenesis. However, specific functional circRNAs in GC remain to be discovered, and their underlying mechanisms remain to be elucidated. METHODS: CircRNAs that were differentially expressed between GC tissues and controls were analyzed using a circRNA microarray dataset. The expression of circVDAC3 in GC was determined using quantitative real-time PCR (qRT-PCR), and the structural features of circVDAC3 were validated. Cell function assays and animal experiments were conducted to explore the effects of circVDAC3 on GC. Finally, bioinformatics analysis, fluorescent in situ hybridization, and dual luciferase assays were used to analyze the downstream mechanisms of circVDAC3. RESULTS: Our results showed that circVDAC3 was downregulated in GC and inhibited the proliferation and metastasis of GC cells. Mechanistically, circVDAC3 acts as a competing endogenous RNA (ceRNA) of miR-592 and deregulates the repression of EIF4E3 by miR-592. EIF4E3 is downregulated in GC and overexpression of miR-592 or knockdown of EIF4E3 in circVDAC3-overexpressing cells weakens the anticancer effect of circVDAC3. CONCLUSION: Our study provides evidence that circVDAC3 affects the growth and metastasis of GC cells via the circVDAC3/miR-592/EIF4E3 axis. Our findings offer valuable insights into the mechanisms underlying GC tumorigenesis and suggest novel therapeutic strategies.

Ultrahigh extinction ratio and a low power silicon thermo-optic switch.

The silicon thermo-optic switch (TOS) is one of the most fundamental and crucial blocks in large-scale silicon photonic integrated circuits (PICs). An energy-efficient silicon TOS with ultrahigh extinction ratio can effectively mitigate cross talk and reduce power consumption in optical systems. In this Letter, we demonstrate a silicon TOS based on cascading Mach-Zehnder interferometers (MZIs) with spiral thermo-optic phase shifters. The experimental results show that an ultrahigh extinction ratio of 58.8 dB is obtained, and the switching power consumption is as low as 2.32 mW/π without silicon air trench. The rise time and fall time of the silicon TOS are about 10.8 and 11.2 µs, respectively. Particularly, the figure of merit (FOM) has been improved compared with previously reported silicon TOS. The proposed silicon TOS may find potential applications in optical switch arrays, on-chip optical delay lines, etc.

Dynamic Arabidopsis P5CS filament facilitates substrate channelling.

In plants, the rapid accumulation of proline is a common response to combat abiotic stress1-7. Delta-1-pyrroline-5-carboxylate synthase (P5CS) is a rate-limiting enzyme in proline synthesis, catalysing the initial two-step conversion from glutamate to proline8. Here we determine the first structure of plant P5CS. Our results show that Arabidopsis thaliana P5CS1 (AtP5CS1) and P5CS2 (AtP5CS2) can form enzymatic filaments in a substrate-sensitive manner. The destruction of AtP5CS filaments by mutagenesis leads to a significant reduction in enzymatic activity. Furthermore, separate activity tests on two domains reveal that filament-based substrate channelling is essential for maintaining the high catalytic efficiency of AtP5CS. Our study demonstrates the unique mechanism for the efficient catalysis of AtP5CS, shedding light on the intricate mechanisms underlying plant proline metabolism and stress response.

Engineering Gene-Specific DNAzymes for Accessible and Multiplexed Nucleic Acid Testing.

The accurate and timely detection of disease biomarkers at the point-of-care is essential to ensuring effective treatment and epidemiological surveillance. Here, we report the selection and engineering of RNA-cleaving DNAzymes that respond to specific genetic markers and amplify detection signals. Because the target-specific activation of gene-specific DNAzymes (gDz) is like the trans-cleavage activity of clustered regularly interspaced short palindromic repeats (CRISPR) CRISPR-associated (Cas) machinery, we further developed a CRISPR-like assay using RNA-cleaving DNAzyme coupled with isothermal sequence and signal amplification (CLARISSA) for nucleic acid detection in clinical samples. Building on the high sequence specificity and orthogonality of gDzs, CLARISSA is highly versatile and expandable for multiplex testing. Upon integration with an isothermal recombinase polymerase amplification, CLARISSA enabled the detection of human papillomavirus (HPV) 16 in 189 cervical samples collected from cervical cancer screening participants (n = 189) with 100% sensitivity and 97.4% specificity, respectively. A multiplexed CLARISSA further allowed the simultaneous analyses of HPV16 and HPV18 in 46 cervical samples, which returned clinical sensitivity of 96.3% for HPV16 and 83.3% for HPV18, respectively. No false positives were found throughout our tests. Besides the fluorescence readout using fluorogenic reporter probes, CLARISSA is also demonstrated to be fully compatible with a visual lateral flow readout. Because of the high sensitivity, accessibility, and multiplexity, we believe CLARISSA is an ideal CRISPR-Dx alternative for clinical diagnosis in field-based and point-of-care applications.

Development of a Decafluorobiphenyl Cyclized Peptide Targeting the NEMO-IKKα/ß Interaction that Enhances Cell Penetration and Attenuates Lipopolysaccharide-Induced Acute Lung Injury.

Aberrant canonical NF-κB signaling has been implicated in diseases, such as autoimmune disorders and cancer. Direct disruption of the interaction of NEMO and IKKα/ß has been developed as a novel way to inhibit the overactivation of NF-κB. Peptides are a potential solution for disrupting protein-protein interactions (PPIs); however, they typically suffer from poor stability in vivo and limited tissue penetration permeability, hampering their widespread use as new chemical biology tools and potential therapeutics. In this work, decafluorobiphenyl-cysteine SNAr chemistry, molecular modeling, and biological validation allowed the development of peptide PPI inhibitors. The resulting cyclic peptide specifically inhibited canonical NF-κB signaling in vitro and in vivo, and presented positive metabolic stability, anti-inflammatory effects, and low cytotoxicity. Importantly, our results also revealed that cyclic peptides had huge potential in acute lung injury (ALI) treatment, and confirmed the role of the decafluorobiphenyl-based cyclization strategy in enhancing the biological activity of peptide NEMO-IKKα/ß inhibitors. Moreover, it provided a promising method for the development of peptide-PPI inhibitors.

Regulatory role of PDK1 via integrated gene analysis of mitochondria-immune response in periodontitis.

AIMS: To investigate the association between mitochondrial events and immune response in periodontitis and related regulatory genes. MAIN METHODS: Gene expression profiles in gingival tissues were retrieved from the Gene Expression Omnibus. Mitochondria-immune response-related differentially expressed genes (MIR-DEGs) between the healthy and periodontitis samples were determined. WGCNA, GO, and KEGG were used to investigate the function and the enriched pathways of MIR-DEGs. The correlation between MIR-DEGs expression and clinical probing pocket depth was analyzed. The MIR-DEGs were further identified and verified in animal samples. A periodontitis model was established in C57BL/6 mice with silk ligation. Micro-computed tomography was used to assess alveolar bone loss. Western blot, quantitative real-time polymerase chain reaction, and immunohistochemical analyses further validated the differential expression of the MIR-DEGs. KEY FINDINGS: A total of ten MIR-DEGs (CYP24A1, PRDX4, GLDC, PDK1, BCL2A1, CBR3, ARMCX3, BNIP3, IFI27, and UNG) were identified, the expression of which could effectively distinguish patients with periodontitis from the healthy controls. Enhanced immune response was detected in the periodontitis group with that in the healthy controls, especially in B cells. PDK1 was a critical MIR-DEG correlated with B cell immune response and clinical periodontal probing pocket depth. Both animal and clinical periodontal samples presented higher gene and protein expression of PDK1 than the control samples. Additionally, PDK1 colocalized with B cells in both animal and clinical periodontal tissues. SIGNIFICANCE: Mitochondria participate in the regulation of the immune response in periodontitis. PDK1 may be the key mitochondria-related gene regulating B-cell immune response in periodontitis.

Short-term postoperative bacteriobilia or fungibilia in liver transplantation patients with donation after circulatory death allografts associated with a longer hospital stay: A single-center retrospective observational study in China.

BACKGROUND: Normal bile is sterile. Studies have shown that cholangitis after liver transplantation (LT) was associated with a relatively poor prognosis. It remains unclear whether the bacteriobilia or fungibilia impact the patient outcomes in LT recipients, especially with donation after circulatory death (DCD) allografts, which was correlated with a higher risk of allograft failure. METHODS: This retrospective study included 139 LT recipients of DCD grafts from 2019 to 2021. All patients were divided into two groups according to the presence or absence of bacteriobilia or fungibilia. The prevalence and microbial spectrum of postoperative bacteriobilia or fungibilia and its possible association with outcomes, especially hospital stay were analyzed. RESULTS: Totally 135 and 171 organisms were isolated at weeks 1 and 2, respectively. Among all patients included in this analysis, 83 (59.7%) developed bacteriobilia or fungibilia within 2 weeks post-transplantation. The occurrence of bacteriobilia or fungibilia (ß = 7.43, 95% CI: 0.02 to 14.82, P = 0.049), particularly the detection of Pseudomonas (ß = 18.84, 95% CI: 6.51 to 31.07, P = 0.003) within 2 weeks post-transplantation was associated with a longer hospital stay. However, it did not affect the graft and patient survival. CONCLUSIONS: The occurrence of bacteriobilia or fungibilia, particularly Pseudomonas within 2 weeks post-transplantation, could influence the recovery of liver function and was associated with prolonged hospital stay but not the graft and patient survival.

Flexible Piezoresistive Sensors Based on PPy Granule-Anchored Multilayer Fibrous Membranes with a Wide Operating Range and High Sensitivity.

The employment of flexible piezoresistive sensors has sparked growing interest within the realm of wearable electronic devices, specifically in the fields of health detection and e-skin. Nevertheless, the advancement of piezoresistive sensors has been impeded by their limited sensitivity and restricted operating ranges. Consequently, it is imperative to fabricate sensors with heightened sensitivity and expanded operating ranges through the utilization of the appropriate methodologies. In this paper, piezoresistive sensors were fabricated utilizing electrospun polyvinylidene fluoride/polyacrylonitrile/polyethylene-polypropylene glycol multilayer fibrous membranes anchored with polypyrrole granules as the sensing layer, while electrospun thermoplastic polyurethane (TPU) fibers were employed as the flexible substrate. The sensitivity of the sensor is investigated by varying the fiber diameter of the sensing layer. The experimental findings reveal that a concentration of 14 wt % in the spinning solution exhibits high sensitivity (996.7 kPa-1) within a wide working range (0-10 kPa). This is attributed to the favorable diameter of the fibers prepared at this concentration, which facilitates the uniform in situ growth of pyrrole. The highly deformable TPU flexible fibers and multilayer sensing layer structure enable different linear responses across a broad pressure range (0-1 MPa). Furthermore, the sensor demonstrates good cyclic stability and can detect human movements under different pressures. These results suggest that the piezoresistive sensor with a wide operating range and high sensitivity has significant potential for future health monitoring and artificial intelligence applications.

Ginseng polysaccharide components attenuate obesity and liver lipid accumulation by regulating fecal microbiota and hepatic lysine degradation.

The increasing incidence of obesity has led to widespread attention in the exploration of natural ingredients. Ginseng polysaccharides (PGP), the main components from Panax ginseng, have been reported potential effect to attenuate obesity and regulate lipid metabolism. In this study, we found that PGP inhibited the high-fat diet (HFD)-induced weight gain, fat ratio and fat tissue weight after 8-week administration. Serum and liver lipid analysis showed that PGP decreased the levels of triglyceride and total cholesterol, which was mediated by the inhibition of key genes for fatty acid and cholesterol metabolisms. Metabolomics studies showed that the inhibitory effect of PGP on liver lipid accumulation was significantly correlated with its regulation of citric acid cycle and lysine degradation. PGP regulated the expression of genes related to lysine degradation in both liver tissue and hepatocytes. In addition, PGP reshaped the composition of fecal microbiota at the genus and species levels in obese mice. Spearman's correlation analysis demonstrated that Staphylococcus sciuri, Staphylococcus lentus, and Pseudoflavonifractor sp. An85 may be the potential targets that PGP maintains the abundance of l-lysine against obesity. It concluded that PGP can attenuate obesity and liver lipid accumulation by regulating fecal microbiota and hepatic lysine degradation.

Ecdysterone improves oxidative damage induced by acute ischemic stroke via inhibiting ferroptosis in neurons through ACSL4.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute ischemic stroke (AIS) is a prominent cause of disability and mortality around the world. Achyranthes bidentata Blume, a regularly prescribed traditional Chinese herb, plays a significant role in traditional Chinese stroke therapy due to its ability to promote blood circulation and remove stasis. Ecdysterone (EDS) is one of the key active components in Achyranthes bidentata Blume, which exhibits antioxidant and anti-cerebral hypoxia properties. However, whether EDS improves AIS and the mechanism of action of AIS is still unclear. AIM OF THE STUDY: The objective of this study was to observe whether EDS ameliorates oxidative damage caused by AIS by inhibiting ferroptosis in neurons via ACSL4. MATERIALS AND METHODS: In vivo, the Middle cerebral artery occlusion (MCAO) rat model was established for research. After treatment with EDS, Neurologic score, TTC, HE and FJC staining were performed, followed by measurements of oxidative stress-related indicators, the content of Fe2+, iron deposition levels and expression of ACSL4, NCOA4 and FTH1 in brain tissue. In vitro, oxygen-glucose deprivation and reperfusion (OGD/R) cell model was established. After treatment with EDS, cell viability, oxidative stress-related indicators, the content of Fe2+ and expression of ACSL4, NCOA4 and FTH1 were detected. In addition, the overexpression of ACSL4 and CETSA technology further elucidated that EDS improves AIS through ACSL4. RESULTS: The results showed that the treatment of EDS could improve the oxidative damage of MCAO rats by inhibiting ferroptosis, and then improve AIS. Importantly, EDS inhibited ferroptosis via ACSL4, thereby inhibiting oxidative stress in MCAO rats or OGD/R-induced PC12 cells. CONCLUSIONS: These results provide evidence that EDS ameliorates oxidative damage caused by AIS by inhibiting ferroptosis via ACSL4, and provide new insights into the potential use of EDS as an effective drug development candidate for AIS.

HNF1A induces glioblastoma by upregulating EPS8 and activating PI3K/AKT signaling pathway.

Despite the exact biological role of HNF1 homolog A (HNF1A) in the regulatory mechanism of glioblastoma (GBM), the molecular mechanism, especially the downstream regulation as a transcription factor, remains to be further elucidated. Immunohistochemistry was used to detect the expression and clinical relevance of HNF1A in GBM patients. CCK8, TUNEL, and subcutaneous tumor formation in nude mice were used to evaluate the effect of HNF1A on GBM in vitro and in vivo. The correction between HNF1A and epidermal growth factor receptor pathway substrate 8 (EPS8) was illustrated by bioinformatics analysis and luciferase assay. Further mechanism was explored that the transcription factor HNF1A regulated the expression of EPS8 and downstream signaling pathways by directly binding to the promoter region of EPS8. Our comprehensive analysis of clinical samples in this study showed that upregulated expression of HNF1A was associated with poor survival in GBM patients. Further, we found that knockdown of HNF1A markedly suppressed the malignant phenotype of GBM cells in vivo and in vitro as well as promoted apoptosis of tumor cells, which was reversed by upregulation of HNF1A. Mechanistically, HNF1A could significantly activate PI3K/AKT signaling pathway by specifically binding to the promoter regions of EPS8. Moreover, overexpression of EPS8 was able to reverse the apoptosis of tumor cells caused by HNF1A knockdown, thereby exacerbating the GBM progression. Correctively, our study has clarified the explicit mechanism by which HNF1A promotes GBM malignancy and provides a new therapeutic target for further clinical application.

Acceptor Copolymerized Axially Chiral Conjugated Polymers with TADF Properties for Efficient Circularly Polarized Electroluminescence.

Chiral conjugated polymer has promoted the development of the efficient circularly polarized electroluminescence (CPEL) device, nevertheless, it remains a challenge to develop chiral polymers with high electroluminescence performance. Herein, by the acceptor copolymerization of axially chiral biphenyl emitting skeleton and benzophenone, a pair of axially chiral conjugated polymers namely R-PAC and S-PAC are synthesized. The target polymers exhibit obvious thermally activated delayed fluorescence (TADF) activities with high photoluminescence quantum yields of 81%. Moreover, the chiral polymers display significant circularly polarized luminescence features, with luminescence dissymmetry factor (|glum|) of nearly 3 × 10-3. By using the chiral polymers as emitters, the corresponding circularly polarized organic light-emitting diodes (CP-OLEDs) exhibit efficient CPEL signals with electroluminescence dissymmetry factor |gEL| of 3.4 × 10-3 and high maximum external quantum efficiency (EQEmax) of 17.8%. Notably, considering both EQEmax and |gEL| comprehensively, the device performance of R-PAC and S-PAC is the best among all the reported CP-OLEDs with chiral conjugated polymers as emitters. This work provides a facile approach to constructing chiral conjugated TADF polymers and discloses the potential of axially chiral conjugated luminescent skeletons in architecting high-performance CP-OLEDs.

Safety and efficacy evaluation of personalized exercise prescription during chemotherapy for lung cancer patients.

BACKGROUND: To explore the safety and effectiveness of personalized exercise intervention during chemotherapy for lung cancer patients who were relatively weak and with compromised cardiopulmonary function. METHODS: Thirty-eight lung cancer patients treated with chemotherapy at Peking University Third Hospital were enrolled in this prospective study. The exercise group (N = 21) received individualized exercise guidance based on personal test results and exercised regularly, while the control group (N = 17) only received exercise education and planed exercise methods according to their own preferences. Both groups underwent three fitness tests and clinical indicator assessments at 0, 6, and 12 weeks after starting the exercise, and the differences in trends of various indicators between the two groups were compared. RESULTS: No exercise-related adverse events occurred during the 12-week exercise period. After 12 weeks of exercise training, in terms of fitness, the exercise group showed significant improvements in 6-min walk test (6MWT) (p < 0.001), peak oxygen consumption (VO2peak) (p = 0.005), muscle content (p < 0.001), muscle percentage (p < 0.001), and grip strength (p = 0.008) compared to the control group. In terms of clinical indicators, the exercise group showed significant improvements in vital capacity (p = 0.018), D-dimer (p = 0.031), and C-reactive protein (CRP) (p = 0.01), uric acid (p = 0.003), triglycerides (p < 0.001), functional average score (p < 0.001), and main symptom average score (p = 0.004) compared to the control group in trends over time. CONCLUSION: Rehabilitation exercises using individualized exercise prescriptions tailored by exercise prescription specialists during chemotherapy are safe for lung cancer patients. Adhering to exercise can achieve comprehensive improvements in physical fitness and quality of life at 12 weeks.

[Factors Influencing Willingness of Farmers to Pay for Agricultural Non-point Source Pollution Control Based on Distributed Cognitive Theory].

The analysis of the willingness of individual farmers to cover costs is an important basis for measuring the economic value of agricultural non-point pollution management， and determining the ecological and economic value of rural surface pollution control is a necessary measure to internalize the externalities of agricultural production. Based on the analysis of the hierarchy of factors influencing the cognition of farmers， this study constructed a theoretical framework based on distributed cognition theory to analyze their willingness to pay for agricultural non-point source pollution control from the perspective of individual farmers. On the basis of this framework， we used the Double-Hurdle model to empirically test the overall process of farmers'willingness to pay and their willingness to pay the amount for agricultural non-point source pollution control by combining 531 microscopic research datapoints in Guanzhong， Shaanxi Province. The results showed that： ① the number of farmers with willingness to pay for agricultural non-point source pollution control was 267， accounting for 50.30% of the total sample， and the average value of willingness to pay was 1 469.77 yuan·hm-2； the total economic value of agricultural non-point source pollution control in Shaanxi Province in 2020 was estimated to be 5.791 billion yuan based on the expected value of the willingness to pay level of the research sample. ② Farmers'willingness to pay for agricultural non-point source pollution control was influenced by the combined effects of personal， regional， and cultural forces， and the effects of each dimension were similar； farmers' willingness to pay for agricultural non-point source pollution control was mainly influenced by the cultural force factor， and the effects of personal and regional forces were very limited. ③ The results of the regressions by income level showed that personal and cultural strengths had a significant impact on the willingness to pay among the low-income group but did not contribute to the increase in the willingness to pay.

Single-cell transcriptome profiling implicates the psychological stress-induced disruption of spermatogenesis.

Male infertility has emerged as a global issue, partly attributed to psychological stress. However, the cellular and molecular mechanisms underlying the adverse effects of psychological stress on male reproductive function remain elusive. We created a psychologically stressed model using terrified-sound and profiled the testes from stressed and control rats using single-cell RNA sequencing. Comparative and comprehensive transcriptome analyses of 11,744 testicular cells depicted the cellular landscape of spermatogenesis and revealed significant molecular alterations of spermatogenesis suffering from psychological stress. At the cellular level, stressed rats exhibited delayed spermatogenesis at the spermatogonia and pachytene phases, resulting in reduced sperm production. Additionally, psychological stress rewired cellular interactions among germ cells, negatively impacting reproductive development. Molecularly, we observed the down-regulation of anti-oxidation-related genes and up-regulation of genes promoting reactive oxygen species (ROS) generation in the stress group. These alterations led to elevated ROS levels in testes, affecting the expression of key regulators such as ATF2 and STAR, which caused reproductive damage through apoptosis or inhibition of testosterone synthesis. Overall, our study aimed to uncover the cellular and molecular mechanisms by which psychological stress disrupts spermatogenesis, offering insights into the mechanisms of psychological stress-induced male infertility in other species and promises in potential therapeutic targets.

Circulating cell-free DNA as a biomarker for diagnosis of Schistosomiasis japonica.

BACKGROUND: Schistosomiasis, a neglected tropical disease, remains an important public health problem. Although there are various methods for diagnosing schistosomiasis, many limitations still exist. Early diagnosis and treatment of schistosomiasis can significantly improve survival and prognosis of patients. METHODOLOGY: Circulating cell-free (cf)DNA has been widely used in the diagnosis of various diseases. In our study, we evaluated the diagnostic value of circulating cfDNA for schistosomiasis caused by Schistosoma japonicum. We focused on the tandem sequences and mitochondrial genes of S. japonicum to identify highly sensitive and specific targets for diagnosis of Schistosomiasis japonica. RESULTS: Through data screening and analysis, we ultimately identified four specific tandem sequences (TD-1, TD-2, TD-3. and TD-4) and six mitochondrial genes (COX1(1), COX1(2), CYTB, ATP6, COX3, and ND5). We designed specific primers to detect the amount of circulating cfDNA in S. japonicum-infected mouse and chronic schistosomiasis patients. Our results showed that the number of tandem sequences was significantly higher than that of the mitochondrial genes. A S. japonicum infection model in mice suggested that infection of S. japonicum can be diagnosed by detecting circulating cfDNA as early as the first week. We measured the expression levels of circulating cfDNA (TD-1, TD-2, and TD-3) at different time points and found that TD-3 expression was significantly higher than that of TD-1 or TD-2. We also infected mice with different quantities of cercariae (20 s and 80 s). The level of cfDNA (TD-3) in the 80 s infection group was significantly higher than in the 20 s infection group. Additionally, cfDNA (TD-3) levels increased after egg deposition. Meanwhile, we tested 42 patients with chronic Schistosomiasis japonica and circulating cfDNA (TD-3) was detected in nine patients. CONCLUSIONS: We have screened highly sensitive targets for the diagnosis of Schistosomiasis japonica, and the detection of circulating cfDNA is a rapid and effective method for the diagnosis of Schistosomiasis japonica. The levels of cfDNA is correlated with cercariae infection severity. Early detection and diagnosis of schistosomiasis is crucial for patient treatment and improving prognosis.

Effect of hydroxyethyl starch on drug stability and release of semaglutide in PLGA microspheres.

The degradation of peptide drugs limits the application of peptide drug microspheres. Structural changes of peptides at the water-oil interface and the destruction of their spatial structure in the complex microenvironment during polymer degradation can affect drug release and in vivo biological activity. This study demonstrates that adding hydroxyethyl starch (HES) to the internal aqueous phase (W1) significantly enhances the stability of semaglutide and optimizes its release behavior in PLGA microspheres. The results showed that this improvement was due to a spontaneous exothermic reaction (ΔH = -132.20 kJ mol-1) facilitated by hydrogen bonds. Incorporating HES into the internal aqueous phase using the water-in-oil-in-water (W1/O/W2) emulsion method yielded PLGA microspheres with a high encapsulation rate of 94.38 %. Moreover, microspheres with HES demonstrated well-controlled drug release over 44 days, unlike the slower and incomplete release in microspheres without HES. The optimized h-MG2 formulation achieved a more complete drug release (83.23 %) and prevented 30.65 % of drug loss compared to the HES-free microspheres within the same period. Additionally, the optimized semaglutide microspheres provided nearly three weeks of glycemic control with adequate safety. In conclusion, adding HES to the internal aqueous phase improved the in-situ drug stability and release behavior of semaglutide-loaded PLGA microspheres, effectively increasing the peptide drug payload in PLGA microspheres.

TiO2/Polystyrene Nanocomposite Antibacterial Material as a Hemoperfusion Adsorbent for Efficient Bilirubin Removal and Prevention of Bacterial Infection.

The use of hemoperfusion adsorbents for the removal of bilirubin in patients with liver failure has become a critical treatment. However, the insufficient clearance of bilirubin and the possibility of bacterial infection during hemoperfusion limit the application. In this work, we designed a novel antibacterial bilirubin adsorbent (PSVT) through the suspension polymerization reaction between double-bond functionalized TiO2 nanoparticles and styrene. PSVT showed an excellent bilirubin adsorption ability and antibacterial performance, ensuring efficient clearance of bilirubin in liver failure patients during hemoperfusion and preventing bacterial infection. The experimental results indicated that TiO2 was uniformly dispersed in the microspheres, which improved the mesoporous structure and increased the specific surface area. Composite adsorbent PSVT showed an exceptional bilirubin adsorption capacity, with the maximum adsorption capacity reaching 24.3 mg/g. In addition, the introduction of TiO2 endowed PSVT with excellent antibacterial ability; the ultimate antibacterial rates against Escherichia coli and Staphylococcus aureus reached 97.31 and 96.47%, respectively. In summary, PSVT served as a novel antibacterial bilirubin adsorbent with excellent bilirubin clearance capacity and antibacterial performance, providing excellent application prospects for treating liver failure patients.