Multi-omics integration highlights the role of ubiquitination in endometriosis fibrosis.

BACKGROUND: Endometriosis, characterized by the presence of active endometrial-like tissues outside the uterus, causes symptoms like dysmenorrhea and infertility due to the fibrosis of endometrial cells, which involves excessive deposition of extracellular matrix (ECM) proteins. Ubiquitination, an important post-transcriptional modification, regulates various biological processes in human diseases. However, its role in the fibrosis process in endometriosis remains unclear. METHODS: We employed multi-omics approaches on two cohorts of endometriosis patients with 39 samples. GO terms and KEGG pathways enrichment analyses were used to investigate the functional changes involved in endometriosis. Pearson's correlation coefficient analysis was conducted to explore the relationship between global proteome and ubiquitylome in endometriosis. The protein expression levels of ubiquitin-, fibrosis-related proteins, and E3 ubiquitin-protein ligase TRIM33 were validated via Western blot. Transfecting human endometrial stroma cells (hESCs) with TRIM33 small interfering RNA (siRNA) in vitro to explore how TRIM33 affects fibrosis-related proteins. RESULTS: Integration of proteomics and transcriptomics showed genes with concurrent change of both mRNA and protein level which involved in ECM production in ectopic endometria. Ubiquitylomics distinguished 1647 and 1698 ubiquitinated lysine sites in the ectopic (EC) group compared to the normal (NC) and eutopic (EU) groups, respectively. Further multi-omics integration highlighted the essential role of ubiquitination in key fibrosis regulators in endometriosis. Correlation analysis between proteome and ubiquitylome showed correlation coefficients of 0.32 and 0.36 for ubiquitinated fibrosis proteins in EC/NC and EC/EU groups, respectively, indicating positive regulation of fibrosis-related protein expression by ubiquitination in ectopic lesions. We identified ubiquitination in 41 pivotal proteins within the fibrosis-related pathway of endometriosis. Finally, the elevated expression of TGFBR1/α-SMA/FAP/FN1/Collagen1 proteins in EC tissues were validated across independent samples. More importantly, we demonstrated that both the mRNA and protein levels of TRIM33 were reduced in endometriotic tissues. Knockdown of TRIM33 promoted TGFBR1/p-SMAD2/α-SMA/FN1 protein expressions in hESCs but did not significantly affect Collagen1/FAP levels, suggesting its inhibitory effect on fibrosis in vitro. CONCLUSIONS: This study, employing multi-omics approaches, provides novel insights into endometriosis ubiquitination profiles and reveals aberrant expression of the E3 ubiquitin ligase TRIM33 in endometriotic tissues, emphasizing their critical involvement in fibrosis pathogenesis and potential therapeutic targets.

Effective enrichment and separation of three flavonoids from Ohwia caudata (Thunberg) H. Ohashi using magnetic layered double hydroxide/ZIF-8 composites and pCEC.

In this study, Fe3O4@ZnCr-layered double hydroxide/zeolitic imidazolate frameworks-8 (MLDH/ZIF-8) magnetically functionalized composites were synthesized by co-precipitation and in situ growth based on the advantages of LDHs and ZIF-8 using Fe3O4 nanoparticles as a magnetic substrate to obtain adsorbents with excellent performance. Moreover, the composite was used for the efficient enrichment of flavonoids in Chinese herbal medicines. The internal structures and surface properties were characterized by SEM, Fourier transform infrared spectroscopy, X-ray diffraction and so on. MLDH/ZIF-8 exhibited a large specific surface area and good paramagnetic properties. The MLDH/ZIF-8 magnetic composite was used as a magnetic solid-phase extraction (MSPE) adsorbent, and a MLDH/ZIF-8 MSPE-pressurized capillary electrochromatography coupling method was developed for the separation and detection of flavonoids (luteolin, kaempferol and apigenin) in a sample of the Chinese herb Ohwia caudata (Thunberg) H. Ohashi. The relevant parameters affecting the extraction efficiency were optimized to determine the ideal conditions for MSPE. 5 mg of adsorbent in sample solution at pH 6, vortex extraction for 5 min, elution with 1.5 mL of ethyl acetate for 15 min. The method showed good linearity in the concentration range of 3-50 µg mL-1 with correlation coefficients of 0.9934-0.9981, and displayed a relatively LODs of 0.07-0.09 µg mL-1. The spiked recoveries of all analytes ranged from 84.5% to 122.0% with RSDs (n=3) between 4.5% and 7.7%. This method is straightforward and efficient, with promising potential in the separation and analysis of active ingredients in various Chinese herbal medicines.

Umbilical Cord Blood and UC-MSCs Combined with Low-Dose Immunosuppressant in the Treatment of Elderly Patients with Pure Red Cell Aplastic: A Case Series.

INTRODUCTION: At present, cyclosporine (CsA) is the first-line treatment for Pure Red Cell Aplasia (PRCA), but CsA administration can be associated with a number of side effects due to its high toxicity. Therefore, it is urgent to explore a safe and effective treatment for elderly patients who cannot be treated with conventional doses of CsA, especially those with multiple complications. Allogeneic Stem Cell Transplantation (ASCT) for PRCA is a promising treatment, but reports of using umbilical cord blood (UCB) are very rare. CASE PRESENTATION: In this report, UCB and umbilical cord mesenchymal stem cells (UC-MSCs) combined with low-dose CsA (1-3mg/kg/d) were used to treat 3 elderly patients who were diagnosed with PRCA combined with multiple complications in heart, lung, and renal. The treatments were successful without complications, and 12 months after stem cell infusion, the blood tests of the patients came normal. Moreover, the function of the liver, heart, and kidney continued to be stable. CONCLUSION: This report provides an effective regimen of using UCB and UC-MSCs combined with low-dose CsA (1-3 mg/kg/d) to treat PRCA, especially for elderly patients with multiple complications who cannot use the conventional dosage.

The effect of instant tea on the aroma of duck meat.

Tea products, such as instant tea, have been shown to improve the aroma of meat products. However, the mechanisms by which tea products enhance meat aroma have not been adequately explained. In this study, we analyzed the impact of instant tea on the aroma of duck meat. Our results showed that treatment with instant tea led to increases in floral, baked, and grassy notes while reducing fishy and fatty notes. Several alcohols, aldehydes, ketones, indole and dihydroactinidiolide exhibited significantly increased OAVs. Conversely, certain saturated aldehydes, unsaturated aldehydes and alcohols displayed significantly decreased OAVs. The enhanced floral, baked and grassy notes were attributed to volatile compounds present in instant tea. The reduction in fishy and fatty notes was linked to polyphenols in instant tea interacting with nonanal, undecanal, (E)-2-octenal, (E)-2-nonenal, (E)-2-decenal, and 2,4-decadienal through hydrophobic interactions and electronic effects. This study enhances our understanding of how tea products improve meat aromas.

Influence of malnutrition according to the glim criteria on the chemotherapy toxicities in patients with advanced lung cancer.

BACKGROUND: Cancer-associated malnutrition is highly prevalent in advanced lung cancer, and 50% of global cancer-related deaths are attributed to cancer-associated malnutrition. Platinum-containing chemotherapy is the standard treatment for advanced lung cancer. Unfortunately, it can cause exacerbated toxicities, which can also have a negative impact on patient's prognosis and quality of life. The Global Leadership Initiative on Malnutrition (GLIM) criteria have been proposed as the world's first accepted diagnostic criteria for malnutrition. However, the effectiveness of GLIM criteria in predicting chemotherapy toxicities in patients with advanced lung cancer is unclear. The aim of this study was to apply the GLIM criteria to assess the prevalence of pre-treatment diagnosis of malnutrition in patients with advanced non-small cell lung cancer (NSCLC) and to determine the impact of nutritional status on patient's chemotherapy toxicity. METHODS: We conducted a study of hospitalized patients with pathologically and clinically diagnosed advanced NSCLC who presented to our hospital from May 2021 to January 2022. Initially, the Nutritional Risk Screening-2002 (NRS-2002) was used for nutritional risk screening, and nutritional status was assessed using the Scored Patient-Generated Subjective Global Assessment (PG-SGA) and GLIM criteria. Chemotherapy toxicity was assessed and graded according to CTCAE5.0, and chemotherapy efficacy was assessed according to RECIST1.1. Kappa test was used to analyze the agreement between PG-SGA and GLIM criteria. Univariate and multivariate logistic regression analyses were used to determine the relationship between malnutrition and chemotherapy toxicity. RESULTS: A total of 215 patients with advanced NSCLC were evaluated for nutritional status. Most of the patients had normal BMI (61.86%) before the start of treatment, 40% were well-nourished as assessed by the PG-SGA tool, and 51.17% were well-nourished as assessed by GLIM criteria. Consistency analysis showed moderate agreement (Kappa = 0.463, P < 0.001) and their correlation was also moderate (Spearman, rs = 0.475, P < 0.001). The objective response rate (ORR) (P = 0.040) and disease control rate (DCR) (P < 0.001) were significantly lower in malnourished patients diagnosed according to GLIM criteria than in well-nourished patients. Multivariate analysis showed that malnutrition (OR = 1.531,95%CI 0.757-3.009; OR = 6.623,95%CI 1.390-31.567, P = 0.046) diagnosed by GLIM criteria was an independent predictor of chemotherapy toxicity. Conclusions Malnutrition diagnosed by GLIM criteria better predicts toxicity during chemotherapy, determines the degree of clinical benefit of chemotherapy, and may affect patient prognosis.

Corrigendum to "Optimization of a tannase-assisted process for obtaining teas rich in theaflavins from Camellia sinensis leaves" [Food Chemistry: X 13 (2022) 100203].

[This corrects the article DOI: 10.1016/j.fochx.2022.100203.].

Analysis of the thickness characteristics of the left atrial posterior wall and its correlation with the low and no voltage areas of the left atrial posterior wall in patients with atrial fibrillation.

OBJECTIVE: To analyze the relationship between the thickness of the left atrial posterior wall and the low and no voltage zones in the left atrial posterior wall in patients with atrial fibrillation (AF). METHODS: 61 patients admitted to our cardiology department for AF and radiofrequency ablation of AF from January 1, 2020 to May 30, 2022 were enrolled according to inclusion and exclusion criteria. The atrial wall thickness was measured by CT scan. Baseline data, preoperative cardiac ultrasound data, preoperative biochemical parameters, low voltage zone (fibrotic zone) and no voltage zone (scar zone) in the left atrial posterior wall area, and various parameters of posterior left atrial wall thickness were collected. RESULTS: The differences of the thickness between the upper, middle and lower mean levels of the left atrial posterior wall were statistically significant (P = 0.004). The results showed that body mass index was weakly positively correlated with the mean level of total left atrial posterior wall thickness (r = 0.426, P = 0.001) and was statistically significant. The remaining indices were positively or negatively correlated with the mean level of total left atrial posterior wall thickness, but none were statistically significant (P > 0.05). CONCLUSIONS: Both left atrial posterior wall low-voltage zone and voltage-free zone were positively correlated with the mean total left atrial posterior wall thickness, and left atrial posterior wall low-voltage zone and voltage-free zone were significantly positively correlated. Body mass index was weakly positively correlated with total left atrial posterior wall thickness.

Radical Three-Component Nitro Spiro-Cyclization of Unsaturated Sulfonamides/Amides to Access NO2-Featured 4-Azaspiro[4.5]decanes.

Free radical three-component nitration/spirocyclization of unsaturated sulfonamides/amides with tert-butyl nitrite was developed for the construction of diverse NO2-revised 4-azaspiro[4.5]decanes. This tandem system featured metal-free participation, simple operation, good selectivity/yields, and a green/low-cost O source. Meanwhile, one nitro-containing complex molecule and a scaled-up operation were performed well to test the synthetic potential of the cascade reaction. Isotopic labeling, radical inhibition experiments, and DFT analysis were carried out to gain insight into the reaction process.

Repeat Surgery after Percutaneous Endoscopic Lumbar Discectomy for Adolescent Lumbar Disc Herniation: A Multicenter Observational Study.

OBJECTIVE: The reported date in the repeat surgical intervention for adolescent lumbar disc herniation (ALDH) after percutaneous endoscopic lumbar discectomy (PELD) was quite scarce. This study aims to introduce cases of repeat surgeries after PELD for ALDH and assess the incidence, chief causes, repeat surgery methods, and surgical outcomes of repeat surgeries after PELD for ALDH. METHODS: A retrospective multicenter observational study was conducted on patients undergoing repeat surgeries after PELD for ALDH at four tertiary referral hospitals from January 2014 through August 2022. The incidence of repeat surgeries, chief causes, strategies for repeat surgeries, and timing of repeat surgeries were recorded and analyzed. The clinical outcomes were evaluated by the Numeric Rating Scales (NRS) scores and the modified MacNab criteria. Statistical analyses were performed with the Wilcoxon signed-rank test. RESULTS: A total of 23 patients who underwent repeat surgeries after PELD for ALDH were included. The chief causes were re-herniation (homo-lateral re-herniation at the same level, new disc herniation of adjacent level). The repeat surgery methods were revision PELD, micro-endoscopic discectomy (MED), open discectomy and instrumented lumbar inter-body fusion. The NRS scores decreased significantly in follow-up evaluations and these scores demonstrated significant improvement at the last follow-up (p < 0.002). For the modified MacNab criteria, at the last follow-up, 18 patients (78.26%) had an excellent outcome, and the overall success rate was 86.95%. CONCLUSION: This study's data suggest that young patients who underwent repeat surgery improved significantly compared to baseline. The chief cause was re-herniation. Revision PELD was the main surgical procedure, which provides satisfactory clinical results in young patients who underwent repeat surgeries.

Metal-free radical bicyclization/chloroalkylarylation of 1,6-enynes with chloroalkanes.

Free radical initiated bicyclization of 1,6-enynes with chloralkanes, is achieved via selective activation of the C(sp3)-H bond of the chloralkane, resulting in diverse polychlorinated/chlorinated polyheterocycles. Two kinds of transformations and a scaled-up experiment were performed to test the synthetic importance of the organic chlorides. Finally, a range of radical inhibition operations and radical clock tests were explored to support the reaction process.

Evaluation of the control efficacy of antagonistic bacteria from V-Ti magnetite mine tailings on kiwifruit brown spots in pot and field experiments.

Seemingly barren heavy-metal-polluted vanadium (V) and titanium (Ti) magnetite mine tailings contain various functional microbes, yet it is unclear whether this includes microbial resources relevant to the biological control of plant diseases. Kiwifruit brown leaf spot disease, caused by Corynespora cassiicola, can seriously reduce kiwifruit yield. To discover effective control measures for kiwifruit leaf spot, 18 bacteria strains among 136 tailing-isolated bacteria from V-Ti magnetite mine tailings were identified as inhibiting C. cassiicola by the confrontation plate method, indicating that antagonistic bacteria surviving in the V-Ti magnetite mine tailings were present at a low level. The 18 antagonistic strains could be divided into two BOX-A1R clusters. The 13 representative strains that were selected for phylogenetic tree construction based on their 16S rRNA sequences belonged to the Bacillus genus. Five predominant strains exhibited different toxin-production times and intensities, with four of them initiating toxin production at 32 h. Among them, Bacillus sp. KT-10 displayed the highest bacteriostatic rate (100%), with a 37.5% growth inhibition rate and an antagonistic band of 3.2 cm against C. cassiicola. Bacillus sp. KT10 also showed a significant inhibitory effect against the expansion speed of kiwifruit brown spots in the pot. The relative control effect was 78.48 and 83.89% at 7 days after the first and last spraying of KT-10 dilution, respectively, confirming a good effect of KT-10 on kiwifruit brown leaf spots in the field. This study demonstrated for the first time that there are some antagonistic bacteria to pathogenic C. cassiicola in V-Ti magnetite mine tailings, and Bacillus sp. KT10 was found to have a good control effect on kiwifruit brown leaf spots in pots and fields, which provided an effective biological control measurement for kiwifruit brown leaf spots.

Treatment of Adhesive Intestinal Obstruction by Nasogastric Tube Under EnhancedRecovery After Surgery: An Efficacy Analysis.

Objective: To explore the application value of enhanced recovery after surgery (ERAS) in the treatment of adhesive intestinal obstruction (AIO) by nasogastric tube (NGT). Methods: Between December 2020 and December 2022, AIO patients who received NGT treatment at The Fourth Hospital of Changsha were selected, including 43 cases receiving ERAS nursing (observation group) and 35 cases receiving routine care (control group). The two groups were compared in terms of postoperative rehabilitation, as well as their psychology, pain, and quality of life which were evaluated using Self-Rating Anxiety/Depression Scale (SAS/SDS), Visual Analogue Scale (VAS), and Short-Form 36 Item Health Survey (SF-36), respectively. During treatment, the adverse reactions were recorded. Results: In the observation group, the abdominal pain and distension relief time, time to first post-treatment flatus and defecation, abdominal circumference reduction 48 hours after admission, bowel sound recovery, first oral food intake, and extubation time were shorter than those of the control group (P < .05), and the SAS and SDS scores were also lower than those of the control group after treatment (P < .05). At 6-24 hours after treatment, the VAS of the observation group was lower than that of the control group, while the SF-36 score was higher (P < .05). Finally, a lower adverse reaction rate was determined in the observation group compared to the control group (P < .05). Conclusions: ERAS care promotes the recovery of AIO patients after NGT treatment, improves their pain and negative emotions, improves their quality of life, and is extremely valuable for clinical application.

Altitude effect on Propofol Pharmacokinetics in Rats.

BACKGROUND: Propofol is an intravenous agent for clinical anesthesia. As the influence of the hypobaric- hypoxic environment (Qinghai-Tibetan region, altitude: 2800-4300 m, PaO2: 15.1-12.4 kPa) on the metabolism of Propofol is complex, the research results on the metabolic characteristics of Propofol in high-altitude areas remain unclear. This study aimed to investigate the pharmacokinetic characteristics of Propofol in a high-altitude hypoxic environment using animal experiments. METHODS: Rats were randomly divided into three groups: high-altitude, medium-altitude, and plain groups. The time of disappearance and recovery of the rat righting reflex was recorded as the time of anesthesia induction and awakening, respectively. The plasma concentration of Propofol was determined by gas chromatography- mass spectrometry. A pharmacokinetic analysis software was used to analyze the blood-drug concentrations and obtain the pharmacokinetic parameters. RESULTS: We observed that when Propofol anesthetizes rats, the anesthesia induction time was shortened, and the recovery time was prolonged with increased altitude. Compared with the plain group, the clearance of Propofol decreased, whereas the half-life, area under the concentration-time curve, peak plasma concentration, and average residence time extension increased. CONCLUSION: The pharmacokinetic characteristics of Propofol are significantly altered in high-altitude hypoxic environments.

High-level production of Rhodiola rosea characteristic component rosavin from D-glucose and L-arabinose in engineered Escherichia coli.

Rosavin is the characteristic component of Rhodiola rosea L., an important medicinal plant used widely in the world that has been reported to possess multiple biological activities. However, the endangered status of wild Rhodiola has limited the supply of rosavin. In this work, we successfully engineered an Escherichia coli strain to efficiently produce rosavin as an alternative production method. Firstly, cinnamate: CoA ligase from Hypericum calycinum, cinnamoyl-CoA reductase from Lolium perenne, and uridine diphosphate (UDP)-glycosyltransferase (UGT) from Bacillus subtilis (Bs-YjiC) were selected to improve the titer of rosin in E. coli. Subsequently, four UGTs from the UGT91R subfamily were identified to catalyze the formation of rosavin from rosin, with SlUGT91R1 from Solanum lycopersicum showing the highest activity level. Secondly, production of rosavin was achieved for the first time in E. coli by incorporating the SlUGT91R1 and UDP-arabinose pathway, including UDP-glucose dehydrogenase, UDP-xylose synthase, and UDP-xylose 4-epimerase, into the rosin-producing stain, and the titer reached 430.5 ± 91.4 mg/L. Thirdly, a two-step pathway derived from L-arabinose, composed of L-arabinokinase and UDP-sugar pyrophosphorylase, was developed in E. coli to further optimize the supply of the precursor UDP-arabinose. Furthermore, 1203.7 ± 32.1 mg/L of rosavin was produced from D-glucose and L-arabinose using shake-flask fermentation. Finally, the production of rosavin reached 7539.1 ± 228.7 mg/L by fed-batch fermentation in a 5-L bioreactor. Thus, the microbe-based production of rosavin shows great potential for commercialization. This work provides an effective strategy for the biosynthesis of other valuable natural products with arabinose-containing units from D-glucose and L-arabinose.

Use of ultrasound to increase the catalytic activity of α-L-rhamnosidase.

α-L-rhamnosidase (Rha) is ubiquitous in nature and has high feasibility in the food and biotechnology industries. A green and environmentally friendly method was used to improve the activity of Rha. Here, we show that the effects of ultrasound treatment on the Rha. Ultrasonic treatment at 80 W for 10 min yielded the highest enzyme activity. Treatment increased enzyme activity by 26.3% and half-life by 124 min. Further, treatment increased the catalytic efficiency of Rha and increased the substrate conversion rate by 33.88%. These results demonstrate that ultrasound increases the catalytic activity and stability of Rha. Thus, ultrasonic treatment of Rha is cost-effective on the industrial scale.

Grain yield and interspecific competition in an oat-common vetch intercropping system at varying sowing density.

Introduction: Oat (Avena nuda L.) and common vetch (Vicia sativa L.) intercropping in the northern regions of China has resulted in substantial production capabilities. However, there is currently a dearth of comprehensive research on whether this intercropping system can enhance productivity through increased sowing densities and underlying interspecies interaction mechanisms. Methods: A two-year field experiment was conducted in 2022 and 2023 to investigate the yield, biological efficiency, economic efficiency, and competition indicators of oats and common vetch in a high-density intercropping system. Two cropping patterns (monocropping and intercropping) and five sowing densities (D1: 4.5×106 plants ha-1; D2:5.4×106 plants ha-1; D3:6.3×106 plants ha-1; D4: 7.2×106 plants ha-1; and D5: 8.1×106 plants ha-1) were arranged in a randomized block design. Results: At the same sowing density, the intercropped oats exhibited greater grain yield than the monocultures. Increasing the oat sowing density significantly enhanced oat yield, with the D3 level in intercropping showing the highest yield increase, ranging from 30.98% to 31.85%, compared with the monoculture. The common vetch intercropping grain yield was maximized in the D2 treatment. The land equivalent ratio was maximized at the D2 level in both years and was significantly higher than D1, with the land equivalent coefficient, system productivity index, and percentage yield difference suggesting that increasing oat sowing densities improved the productivity of the intercropping system, with the best performance observed at the D2 level. For both years, the proportionate actual yield loss of oat was the highest at the D3 level; significantly surpassing D1, proportionate actual yield loss of common vetch and actual yield loss were the highest at level D2, both significantly surpassing D1. These indicates that appropriate densification contributes to the realization of the advantages of intercropping. With an increased oat sowing density, the economic benefits of the intercropping system were maximized at the D2 and D3 levels. Regarding intercropping competition, oat was the dominant crop under different sowing densities (Aggressivity for oat (AO)>0, relative crowding coefficient for oat (KO)>1, competition ratio for oat (CRO)>1), whereas common vetch was the inferior crop. Compared with the D1 level, the D2 level harmonized the aggressivity, competitive ratio, and relative crowding coefficients of oat and common vetch, significantly increasing crowding coefficient for common vetch (KV) and competition ratio for common vetch by 19.76% to 21.94% and 4.80% to 7.51%, respectively, while reducing KO and CRO. Discussion: This result suggests that in the intercropping of common vetch and oat in alpine regions, rational densification can harmonize interspecific competition and thus improve the biological efficiency and economic benefits of intercropping systems.

A Suture Technique for Ruptured Annulus Fibrosus Following Decompression Under Percutaneous Transforaminal Endoscopic Discectomy.

The suture technique for a ruptured annulus fibrosus (AF) under full-endoscopy remains challenging. Direct suturing of a ruptured annular tear after full decompression has been shown to decrease the recurrence rate of lumbar disc herniation during endoscopic surgery. Traditional suture operations under endoscopy involve only simple suturing of the ruptured AF. Due to the weak and poor quality of the AF tissue around the tear portal, using this area as needle insertion points during suturing may lead to insufficient tension and a low success rate of AF closure. Currently, there is no detailed technical illustration based on video for AF tear suturing under lumbar full-endoscopy. We innovatively propose a method of covering and suturing the AF tear by pulling up the posterior longitudinal ligament (PLL) under lumbar endoscopy and using three stitches (PLL-AF suture technique). The patient who received the novel suture technique achieved satisfactory results. Six months after the operation, lumbar MRI showed no evidence of recurrence in the outpatient clinic.

Determination of Aminophylline in Human Serum Using Hydrogel Microspheres for Coupled Surface-Enhanced Raman Spectroscopy (SERS) and Solid-Phase Extraction.

Aminophylline (AMP) is a bronchodilator. The therapeutic and toxic doses are very close. Therefore, therapeutic drug monitoring (TDM) of AMP is essential in clinical practice. Microgels were synthesized by free radical precipitation polymerization. Silver@poly(N-isopropyl acrylamide) (Ag@PNIPAM) hybrid microgels were obtained by loading silver (Ag) nanoparticles into the three-dimensional network of the microgels by in situ reduction. The microgel is a three-dimensional reticular structure with tunable pore size, large specific surface area, and good biocompatibility, which can be used as a sorbent for solid-phase extraction (SPE) of target molecules in complex matrices and as a surface-enhanced Raman spectroscopy (SERS) substrate. We optimized the conditions affecting SERS enhancement, such as silver nitrate (AgNO3) concentration and SPE time, according to the SERS strategy of Ag@PNIPAM hybrid microgels to achieve label-free TDM for trace AMP in human serum. The results showed good linearity between the logarithmic concentration of AMP and its SERS intensity in the range of 1-1.1 × 102 µg/mL, with a correlation coefficient (R2) of 0.9947 and a low detection limit of 0.61 µg/mL. The assay accuracy was demonstrated by spiking experiments, with recoveries ranging from 93.0 to 101.8%. The method is rapid, sensitive, reproducible, requires simple sample pretreatment, and has good potential for use in clinical treatment drug monitoring.

Ultrasensitive measurement of tactile force based on a PDMS-embedded microfiber Mach-Zehnder interferometer.

This study investigates the utilization of an in-fiber interferometer embedded in polydimethylsiloxane (PDMS) to develop a highly sensitive tactile sensor. The tapered mode-field mismatch structure is more conducive to stimulating strong high order modes to promote the sensitivity of the sensor. Experimental investigations are conducted to study the sensing performance of the sensor, resulting in a sensitivity of 23.636 nm/N and a detection limit of 0.746 mN. The experiments demonstrate that employing fast Fourier transform (FFT) and inverse FFT (IFFT) methods to filter weak high order modes significantly improves the repeatability of the sensor, resulting in a repeatability error of less than 1%.

Regulating protein corona on nanovesicles by glycosylated polyhydroxy polymer modification for efficient drug delivery.

The dynamic protein corona formed on nanocarriers has been revealed to strongly affect their in vivo behaviors. Precisely manipulating the formation of protein corona on nanocarriers may provide an alternative impetus for specific drug delivery. Herein, we explore the role of glycosylated polyhydroxy polymer-modified nanovesicles (CP-LVs) with different amino/hydroxyl ratios in protein corona formation and evolution. CP-LVs with an amino/hydroxyl ratio of approximately 0.4 (CP1-LVs) are found to efficiently suppress immunoglobulin adsorption in blood and livers, resulting in prolonged circulation. Moreover, CP1-LVs adsorb abundant tumor distinctive proteins, such as CD44 and osteopontin in tumor interstitial fluids, mediating selective tumor cell internalization. The proteins corona transformation specific to the environment appears to be affected by the electrostatic interaction between CP-LVs and proteins with diverse isoelectric points. Benefiting from surface modification-mediated protein corona regulation, paclitaxel-loaded CP1-LVs demonstrate superior antitumor efficacy to PEGylated liposomes. Our work offers a perspective on rational surface-design of nanocarriers to modulate the protein corona formation for efficient drug delivery.