Comparative understanding of peroxide quantitation assays: a case study with peptide drug product degradation.

Peroxide-mediated oxidation of drug molecules is a known challenge faced throughout the pharmaceutical development pathway-from early-stage stability studies to manufacturing processes. During the initial development stage, the major source of peroxide is the formulation excipients, whether they are pre-loaded or generated in situ due to slow degradation, and in the late phase, peroxides can be introduced during sanitization processes or generated via cavitation. In essence, a control strategy for peroxide mitigation often becomes a critical quality attribute for successful drug development. To this end, quantitation of peroxide is essential to monitor the peroxide level to ensure product quality and proposed shelf-life. However, methods for reliable and robust quantitation to detect trace levels of peroxide in a complex drug product matrix become increasingly challenging. This article discusses three high-throughput assays based on absorbance, fluorescence and chemiluminescence measurements to detect peroxide at a low level and compares the methods through validation studies in water. Selected methods have also been tested to understand the forced degradation of model peptide drug products with spiked hydrogen peroxide. Peptide degradation profiles and residual peroxide levels are presented to provide an understanding of the suitability of the quantitation methods and their performance.

Effect of carbon nanoparticle suspension injection versus indocyanine green tracer in guiding lymph node dissection during radical gastrectomy (FUTURE-01): a randomized clinical trial.

BACKGROUND: Carbon nanoparticle suspension injection (CNSI) and indocyanine green (ICG) have both been applied intraoperatively to facilitate lymphatic mapping and postoperatively to sort lymph nodes (LNs) in gastric cancer patients. However, no study has compared the two tracers in gastric cancer patients. MATERIALS AND METHODS: This prospective randomized controlled trial was conducted from January 2022 to March 2023. Patients with potentially resectable gastric cancer (cT1-4a N0/+ M0) were randomized to the CNSI or ICG group. RESULTS: This study enrolled 96 patients. Ninety patients were in the modified intention-to-treat population, including 46 patients (32 males and 14 females; mean [SD] age, 57.4 [9.4] years) in the CNSI group and 44 patients (31 males and 13 females; mean [SD] age, 60.8 [8.8] years) in the ICG group. The mean (SD) number of retrieved LNs was 69.8 (21.9) and 53.6 (17.2) in the CNSI and ICG groups, respectively (P<0.001). The mean (SD) number of retrieved micro-LNs was 19.9 (13.3) and 11.6 (9.9) in the CNSI and ICG groups, respectively (P=0.001). The mean (SD) number of metastatic LNs was 8.1 (11.9) and 5.2 (9.2) in the CNSI and ICG groups, respectively (P=0.19). CONCLUSIONS: Compared with ICG, CNSI can increase the number of LNs detected, especially micro-LNs. Both tracers have high diagnostic value for detecting metastatic LNs. CNSI-guided lymphography may be a superior method for improving the accuracy of LN dissection.

Assessing Morinidazole for Surgical Site Infection in Class â ¢ Wounds Prevention: A Multicenter, Randomized, Single-Blind, Parallel-Controlled Study.

INTRODUCTION: Surgical site infections are significant postoperative risks, antibiotic prophylaxis is crucial due to the presence of anaerobic bacteria. This study investigated the efficacy and safety of a novel nitroimidazole, morinidazole, in SSI reduction in class Ⅲ wounds, as there is currently a lack of evidence in the existing literature. METHODS: A multicenter randomized clinical trial was conducted from December 2020 to October 2022 in the general surgery departments of 12 tertiary hospitals in China. 459 patients in two treatment groups using morinidazole plus ceftriaxone or ceftriaxone alone. Efficacy and safety were evaluated including SSI incidence, adverse events, and compliance. Statistical analysis employed SAS 9.4 software. Data analysis was performed from February to May 2023. RESULTS: A total of 440 participants (median [IQR] age, 63.0 [54.0, 70.0] years; 282 males [64.09%]; 437 patients were of Han race [99.32%]) were randomized. The experimental group exhibited a significantly lower SSI rate compared with the control group (31 [14.49%] vs 52 [23.01%]; risk difference, 1.76%, 95%CI, 1.08% to 2.88%; P=0.0224). The superficial incisional site infections revealed a marked reduction in the experimental group (12 [5.61%] vs 31 [13.37%]; risk difference,2.68%; 95%CI,1.34%to5.36%; P=0.0042). Non-surgical site infections, severe postoperative complications, and total adverse events showed no statistically significant differences between the groups (P>0.05). CONCLUSION: The significant decrease in SSI rates and superficial incisional infections demonstrates morinidazole as a valuable prophylactic antibiotic. Our findings provided valuable insights for clinical practice, where this new-generation nitroimidazole can play a crucial role in SSI prevention.

Predictive value of neutrophil-to-lymphocyte ratio in coronary chronic total occlusion patients.

BACKGROUND: The neutrophil to lymphocyte ratio (NLR) has been reported as a novel predictor for atherosclerosis and cardiovascular outcomes. This study aimed to determine the effects of NLR on long-term clinical outcomes of chronic total occlusion (CTO) patients. METHODS: A total of 670 patients with CTO who met the inclusion criteria were included at the end of the follow-up period. Patients were divided into tertiles according to their baseline NLR levels at admission: low (n = 223), intermediate (n = 223), and high (n = 224). The incidence of major adverse cardiac events (MACEs) during the follow-up period, including all-cause death, nonfatal myocardial infarction (MI), or ischemia-driven revascularization, were compared among the three groups. RESULTS: Major adverse cardiac events were observed in 27 patients (12.1%) in the low tertile, 40 (17.9%) in the intermediate tertile, and 61 (27.2%) in the high NLR tertile (P < 0.001). Kaplan-Meier analysis demonstrated a significantly higher incidence of MACE, ischemia-driven coronary revascularization, non-fatal MI, and mortality in patients within the high tertile than those in the low and intermediate groups (all P < 0.001). Multivariable COX regression analysis showed that the high tertile of baseline NLR level showed a strong association with the risk of MACE (hazard ratio [HR] = 2.21; 95% confidence interval [CI]: 1.21-4.03; P = 0.009), ischemia-driven coronary revascularization (HR = 3.19; 95% CI: 1.56-6.52; P = 0.001), MI (HR = 2.61; 95% CI: 1.35-5.03; P = 0.043) and mortality (HR = 3.78; 95% CI: 1.65-8.77; P = 0.001). CONCLUSION: Our findings suggest that NLR is an inexpensive and readily available biomarker that can independently predict cardiovascular risk in patients with CTO.

Two-Dimensional GeS/SnSe2 Tunneling Photodiode with Bidirectional Photoresponse and High Polarization Sensitivity.

A two-dimensional (2D) broken-gap (type-III) p-n heterojunction has a unique charge transport mechanism because of nonoverlapping energy bands. In light of this, type-III band alignment can be used in tunneling field-effect transistors (TFETs) and Esaki diodes with tunable operation and low consumption by highlighting the advantages of tunneling mechanisms. In recent years, 2D tunneling photodiodes have gradually attracted attention for novel optoelectronic performance with a combination of strong light-matter interaction and tunable band alignment. However, an in-depth understanding of the tunneling mechanisms should be further investigated, especially for developing electronic and optoelectronic applications. Here, we report a type-III tunneling photodiode based on a 2D multilayered p-GeS/n+-SnSe2 heterostructure, which is first fabricated by the mechanical exfoliation and dry transfer method. Through the Simmons approximation, its various tunneling transport mechanisms dependent on bias and light are demonstrated as the origin of excellent bidirectional photoresponse performance. Moreover, compared to the traditional p-n photodiode, the device enables bidirectional photoresponse capability, including maximum responsivity values of 43 and 8.7 A/W at Vds = 1 and -1 V, respectively, with distinctive photoactive regions from the scanning photocurrent mapping. Noticeably, benefiting from the in-plane anisotropic structure of GeS, the device exhibits an enhanced photocurrent anisotropic ratio of 9, driven by the broader depletion region at Vds = -3 V under 635 nm irradiation. Above all, the results suggest that our designed architecture can be potentially applied to CMOS imaging sensors and polarization-sensitive photodetectors.

Efficacy and safety of topical clobetasol propionate in comparison with alternative treatments in oral lichen planus: an updated systematic review and meta-analysis.

Background: Oral lichen planus (OLP) is a relatively common chronic T cell-mediated disease characterized by pain and inflammation. Clobetasol propionate (CLO) is the first-line drug in the treatment of OLP. The meta-analysis aimed to evaluate the efficacy and safety of CLO for treating patients with OLP. Methods: PubMed, Embase and Web of Science were systematically searched from the database inception date up to August 2023. There were no restrictions on language or date of publication. The outcomes of our interest were as follows: improvement of clinical signs and/or symptoms, total lesion size, relapse and adverse events. Results: A total of 17 RCTs evaluating the effects of CLO were included in this study. The results revealed no significant difference in the clinical score (WMD = 0.14, 95% CI: -0.39, 0.66; p = 0.609) and pain score (WMD = 0.17, 95% CI: -0.44, 0.79; p = 0.582) between CLO and other treatments. However, clinical resolution (RR = 1.61, 95% CI: 1.17, 2.22; p = 0.003) and symptoms improvement (RR = 1.80, 95% CI: 1.17, 2.77; p = 0.008) were significantly different between CLO and other treatments. Moreover, there was a significant reduction in the total lesion size with CLO treatment (WMD = -0.58, 95% CI: -1.03, -0.13; p = 0.011). In addition, CLO showed no statistical incidence of adverse events (RR = 1.46, 95% CI: 0.86, 2.50; p = 0.161) and relapse (RR = 1.56, 95% CI: 0.66, 3.71; p = 0.314) than other therapies. Conclusion: This systematic review and meta-analysis of 17 randomized clinical trials supported the long-term application of CLO as an effective regimen in OLP patients.

Two new species of Bamazomus Harvey, 1992 from southern China (Schizomida, Hubbardiidae).

Two new schizomid species belonging to Bamazomus Harvey, 1992 are described from China: B.shanghang sp. nov. (♂♀) from Fujian Province and B.songi sp. nov. (♂♀) from Guangdong Province. In addition to their descriptions, illustrations and diagnoses, a distribution map is provided. These are first Bamazomus species from the mainland China and the northernmost in continental Asia.

Novel insights into the glucose metabolic alterations of freshwater snails: a pathway to molluscicide innovation and snail control strategies.

As ecosystem disruptors and intermediate hosts for various parasites, freshwater snails have significant socioeconomic impacts on human health, livestock production, and aquaculture. Although traditional molluscicides have been widely used to mitigate these effects, their environmental impact has encouraged research into alternative, biologically based strategies to create safer, more effective molluscicides and diminish the susceptibility of snails to parasites. This review focuses on alterations in glucose metabolism in snails under the multifaceted stressors of parasitic infections, drug exposure, and environmental changes and proposes a novel approach for snail management. Key enzymes within the glycolytic pathway, such as hexokinase and pyruvate kinase; tricarboxylic acid (TCA) cycle; and electron transport chains, such as succinate dehydrogenase and cytochrome c oxidase, are innovative targets for molluscicide development. These targets can affect both snails and parasites and provide an important direction for parasitic disease prevention research. For the first time, this review summarises the reverse TCA cycle and alternative oxidase pathway, which are unique metabolic bypasses in invertebrates that have emerged as suitable targets for the formulation of low-toxicity molluscicides. Additionally, it highlights the importance of other metabolic pathways, including lactate, alanine, glycogenolysis, and pentose phosphate pathways, in snail energy supply, antioxidant stress responses, and drug evasion mechanisms. By analysing the alterations in key metabolic enzymes and their products in stressed snails, this review deepens our understanding of glucose metabolic alterations in snails and provides valuable insights for identifying new pharmacological targets.

Laser Precise Synthesis of Oxidation-Free High-Entropy Alloy Nanoparticle Libraries.

High-entropy alloy nanoparticles (HEA-NPs) show exceptional properties and great potential as a new generation of functional materials, yet a universal and facile synthetic strategy in air toward nonoxidized and precisely controlled composition remains a huge challenge. Here we provide a laser scribing method to prepare single-phase solid solution HEA-NPs libraries in air with tunable composition at the atomic level, taking advantage of the laser-induced metastable thermodynamics and substrate-assisted confinement effect. The three-dimensional porous graphene substrate functions as a microreactor during the fast heating/cooling process, which is conductive to the generation of the pure alloy phase by effectively blocking the binding of oxygen and metals, but is also beneficial for realizing accurate composition control via microstructure confinement-endowed favorable vapor pressure. Furthermore, by combining an active learning approach based on an adaptive design strategy, we discover an optimal composition of quinary HEA-NP catalysts with an ultralow overpotential for Li-CO2 batteries. This method provides a simple, fast, and universal in-air route toward the controllable synthesis of HEA-NPs, potentially integrated with machine learning to accelerate the research on HEAs.

CsMIEL1 effectively inhibits the accumulation of anthocyanins under low temperatures in tea plants (Camelliasinensis).

Tea is one of the most prevalent non-alcoholic beverages. The leaves of tea plants hyperaccumulate anthocyanins under cold stress, resulting in enhanced bitterness. Previously, we determined that the RING-type E3 ubiquitin ligase CsMIEL1 from the tea plant (Camellia sinensis (L.) O. Kuntze) is involved in the response to stress conditions. This study aimed to determine the role of CsMIEL1 in anthocyanin accumulation at the post-translational modification level. The results showed that the heterologous expression of CsMIEL1 led to an 86% decrease in anthocyanin levels, resulting in a significant decrease in the mRNA levels of related genes in Arabidopsis at low temperatures but no significant differences in other phenotypes. Furthermore, multi-omics analysis and yeast two-hybrid library screening were performed to identify potential downstream targets of CsMIEL1. The results showed that the overexpression of CsMIEL1 resulted in 45% (448) of proteins being differentially expressed, of which 8% (36) were downregulated in A.thaliana, and most of these differentially expressed proteins (DEPs) were clustered in the plant growth and secondary metabolic pathways. Among the 71 potential targets that may interact with CsMIEL1, CsMYB90 and CsGSTa, which are related to anthocyanin accumulation, were selected. In subsequent analyses, these two proteins were verified to interact with CsMIEL1 via yeast two-hybrid (Y2H) and pull-down analyses in vitro. In summary, we explored the potential mechanism by which the E3 ligase relieves anthocyanin hyperaccumulation at low temperatures in tea plants. These results provide a new perspective on the mechanisms of anthocyanin regulation and the molecular breeding of tea plants.

Real-world effectiveness of a new powered stapling system with gripping surface technology on the intraoperative clinical and economic outcomes of gastrectomy for gastric cancer.

BACKGROUND: Surgical staplers have been widely used to facilitate surgeries, and this study aimed to examine the real-world effectiveness of a new powered stapling system with Gripping Surface Technology (GST) on intraoperative outcomes of gastrectomy for gastric cancer. METHOD: The data were extracted from the Fourth Hospital of Hebei Medical University's (FHHMU) medical records system. Participants (N = 121 patients) were classified into the GST (n = 59) or non-GST group (n = 62), based on the use of the GST system. The intraoperative outcomes such as bleeding were assessed by reviewing video records. T-tests, Chi-square tests, and Mann-Whitney-U tests were used to compare the baseline characteristics between groups. Multivariate logistic regression was conducted for adjusting outcomes to study the effect of variables. RESULTS: Compared with the non-GST group, the GST group had significantly lower risks for intraoperative bleeding, intraoperative anastomosis intervention rate, intraoperative suture, and intraoperative pression (aORs: 0.0853 (p < 0.0001), 0.076 (p = 0.0003), 0.167 (p = 0.0012), and 0.221 (p = 0.0107), respectively). The GST group also consumed one fewer cartridge than the non-GST group (GST:5 vs non-GST: 6, p = 0.0241). CONCLUSION: The use of the GST system was associated with better intraoperative outcomes and lower cartridge consumption in Chinese real-world settings.

Identifying the risk factors of ICU-acquired fungal infections: clinical evidence from using machine learning.

Background: Fungal infections are associated with high morbidity and mortality in the intensive care unit (ICU), but their diagnosis is difficult. In this study, machine learning was applied to design and define the predictive model of ICU-acquired fungi (ICU-AF) in the early stage of fungal infections using Random Forest. Objectives: This study aimed to provide evidence for the early warning and management of fungal infections. Methods: We analyzed the data of patients with culture-positive fungi during their admission to seven ICUs of the First Affiliated Hospital of Chongqing Medical University from January 1, 2015, to December 31, 2019. Patients whose first culture was positive for fungi longer than 48 h after ICU admission were included in the ICU-AF cohort. A predictive model of ICU-AF was obtained using the Least Absolute Shrinkage and Selection Operator and machine learning, and the relationship between the features within the model and the disease severity and mortality of patients was analyzed. Finally, the relationships between the ICU-AF model, antifungal therapy and empirical antifungal therapy were analyzed. Results: A total of 1,434 cases were included finally. We used lasso dimensionality reduction for all features and selected six features with importance ≥0.05 in the optimal model, namely, times of arterial catheter, enteral nutrition, corticosteroids, broadspectrum antibiotics, urinary catheter, and invasive mechanical ventilation. The area under the curve of the model for predicting ICU-AF was 0.981 in the test set, with a sensitivity of 0.960 and specificity of 0.990. The times of arterial catheter (p = 0.011, OR = 1.057, 95% CI = 1.053-1.104) and invasive mechanical ventilation (p = 0.007, OR = 1.056, 95%CI = 1.015-1.098) were independent risk factors for antifungal therapy in ICU-AF. The times of arterial catheter (p = 0.004, OR = 1.098, 95%CI = 0.855-0.970) were an independent risk factor for empirical antifungal therapy. Conclusion: The most important risk factors for ICU-AF are the six time-related features of clinical parameters (arterial catheter, enteral nutrition, corticosteroids, broadspectrum antibiotics, urinary catheter, and invasive mechanical ventilation), which provide early warning for the occurrence of fungal infection. Furthermore, this model can help ICU physicians to assess whether empiric antifungal therapy should be administered to ICU patients who are susceptible to fungal infections.

Comparative analysis of two digestive tract reconstruction methods in total laparoscopic radical total gastrectomy.

BACKGROUND: The incidence of gastric cancer has significantly increased in recent years. Surgical resection is the main treatment, but the method of digestive tract reconstruction after gastric cancer surgery remains controversial. In the current study, we sought to explore a reasonable method of digestive tract reconstruction and improve the quality of life and nutritional status of patients after surgery. To this end, we statistically analyzed the clinical results of patients with gastric cancer who underwent jejunal interposition double-tract reconstruction (DTR) and esophageal jejunum Roux-en-Y reconstruction (RY). AIM: To explore the application effect of DTR in total laparoscopic radical total gastrectomy (TLTG) and evaluate its safety and efficacy. METHODS: We collected the relevant data of 77 patients who underwent TLTG at the Fourth Hospital of Hebei Medical University from October 2021 to January 2023. Among them, 35 cases were treated with DTR, and the remaining 42 cases were treated with traditional RY. After 1:1 propensity score matching, the cases were grouped into 31 cases per group, with evenly distributed data. The clinical characteristics and short- and long-term clinical outcomes of the two groups were statistically analyzed. RESULTS: The two groups showed no significant differences in basic data, intraoperative blood loss, number of lymph node dissections, first defecation time after operation, postoperative hospital stay, postoperative complications, and laboratory examination results on the 1st, 3rd, and 5th days after operation. The operation time of the DTR group was longer than that of the RY group [(307.58 ± 65.14) min vs (272.45 ± 62.09) min, P = 0.016], but the first intake of liquid food in the DTR group was shorter than that in the RY group [(4.45 ± 1.18) d vs (6.0 ± 5.18) d, P = 0.028]. The incidence of reflux heartburn (Visick grade) and postoperative gallbladder disease in the DTR group was lower than that in the RY group (P = 0.033 and P = 0.038). Although there was no significant difference in body weight, hemoglobin, prealbumin, and albumin between the two groups at 1,3 and 6 months after surgery, the diet of patients in the DTR group was better than that in the RY group (P = 0.031). CONCLUSION: The clinical effect of DTR in TLTG is better than that of RY, indicating that it is a more valuable digestive tract reconstruction method in laparoscopic gastric cancer surgery.

Tick-borne bacterial agents in Hyalomma asiaticum ticks from Xinjiang Uygur Autonomous Region, Northwest China.

BACKGROUND: Hyalomma ticks are widely distributed in semi-arid zones in Northwest China. They have been reported to harbor a large number of zoonotic pathogens. METHODS: In this study, a total of 334 Hyalomma asiaticum ticks infesting domestic animals were collected from four locations in Xinjiang, Northwest China, and the bacterial agents in them were investigated. RESULTS: A putative novel Borrelia species was identified in ticks from all four locations, with an overall positive rate of 6.59%. Rickettsia sibirica subsp. mongolitimonae, a human pathogen frequently reported in Europe, was detected for the second time in China. Two Ehrlichia species (Ehrlichia minasensis and Ehrlichia sp.) were identified. Furthermore, two Anaplasma species were characterized in this study: Candidatus Anaplasma camelii and Anaplasma sp. closely related to Candidatus Anaplasma boleense. It is the first report of Candidatus Anaplasma camelii in China. CONCLUSIONS: Six bacterial agents were reported in this study, many of which are possible or validated pathogens for humans and animals. The presence of these bacterial agents may suggest a potential risk for One Health in this area.

Genetic causal relationship between immune diseases and migraine: a Mendelian randomization study.

Background: Migraine has an increased prevalence in several immune disorders, but genetic cause-effect relationships remain unclear. Mendelian randomization (MR) was used in this study to explore whether immune diseases are causally associated with migraine and its subtypes. Methods: We conducted a two-sample bidirectional multivariate Mendelian randomization study. Single-nucleotide polymorphisms (SNP) for six immune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1D), allergic rhinitis (AR), asthma and psoriasis, were used as genetic instrumental variables. Summary statistics for migraine were obtained from 3 databases: the International Headache Genetics Consortium (IHGC), UK Biobank, and FinnGen study. MR analyses were performed per outcome database for each exposure and subsequently meta-analyzed. Reverse MR analysis was performed to determine whether migraine were risk factors for immune diseases. In addition, we conducted a genetic correlation to identify shared genetic variants for these two associations. Results: No significant causal relationship was found between immune diseases and migraine and its subtypes. These results were robust with a series of sensitivity analyses. Using the linkage disequilibrium score regression method (LDSC), we detected no genetic correlation between migraine and immune diseases. Conclusion: The evidence from our study does not support a causal relationship between immune diseases and migraine. The mechanisms underlying the frequent comorbidity of migraine and several immune diseases need to be further elucidated.

2D Free-Standing GeS1-xSex with Composition-Tunable Bandgap for Tailored Polarimetric Optoelectronics.

Germanium-based monochalcogenides (i.e., GeS and GeSe) with desirable properties are promising candidates for the development of next-generation optoelectronic devices. However, they are still stuck with challenges, such as relatively fixed electronic band structure, unconfigurable optoelectronic characteristics, and difficulty in achieving free-standing growth. Herein, it is demonstrated that two-dimensional (2D) free-standing GeS1-xSex (0 ≤ x ≤ 1) nanoplates can be grown by low-pressure rapid physical vapor deposition (LPRPVD), fulfilling a continuously composition-tunable optical bandgap and electronic band structure. By leveraging the synergistic effect of composition-dependent modulation and free-standing growth, GeS1-xSex-based optoelectronic devices exhibit significantly configurable hole mobility from 6.22 × 10-4 to 1.24 cm2V-1s⁻1 and tunable responsivity from 8.6 to 311 A W-1 (635 nm), as x varies from 0 to 1. Furthermore, the polarimetric sensitivity can be tailored from 4.3 (GeS0.29Se0.71) to 1.8 (GeSe) benefiting from alloy engineering. Finally, the tailored imaging capability is also demonstrated to show the application potential of GeS1-xSex alloy nanoplates. This work broadens the functionality of conventional binary materials and motivates the development of tailored polarimetric optoelectronic devices.

Plantaginis semen ameliorates diabetic kidney disease via targeting the sphingosine kinase 1/sphingosine-1-phosphate pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Plantaginis Semen (PS) is widely utilized as a common herb in several Asian countries, particularly China, due to its diuretic, anti-hypertensive, anti-hyperlipidemic, and anti-hyperglycemic properties. Furthermore, it is acknowledged for its ability to mitigate renal complications associated with metabolic syndrome. Despite its extensive usage, there is limited systematic literature elucidating its therapeutic mechanisms, thus emphasizing the necessity for comprehensive investigations in this field. AIM: This study aims to comprehensively evaluate the therapeutical potential of PS in treating diabetic kidney disease (DKD) and to elucidate the underlying mechanisms through in vivo and in vitro models. METHODS: The main composition of PS were characterized using the UPLC-QTOF-MS method. For the in vivo investigation, a mouse model mediated by streptozocin (STZ) associated with a high-fat diet (HFD) and unilateral renal excision was established. The mice were split into 6 groups (n = 8): control group (CON group), DKD group, low-dose of Plantago asiatica L. seed extract group (PASE-L group, 3 g/kg/d), medium-dose of PASE group (PASE-M, 6 g/kg/d), high-dose of PASE group (PASE-H, 9 g/kg/d), and positive drug group (valsartan, VAS group, 12 mg/kg/d). After 8 weeks of treatment, the damage induced by DKD was evaluated by using relevant parameters of urine and blood. Furthermore, indicators of inflammation and factors associated with the SphK1-S1P signaling pathway were investigated. For the in vitro study, the cell line HBZY-1 was stimulated by high glucose (HG), they were then co-cultured with different concentrations of PASE, and the corresponding associated inflammatory and sphingosine kinase 1/sphingosine-1-phosphate (SphK1-S1P) factors were examined. RESULTS: A total of 59 major components in PS were identified, including flavonoids, iridoids, phenylethanol glycosides, guanidine derivatives, and fatty acids. In the mouse model, PS was found to significantly improve body weight, decrease fasting blood glucose (FBG) levels, increased glucose tolerance and insulin tolerance, improved kidney-related markers compared to the DKD group, pathological changes in the kidneys also improved dramatically. These effects showed a dose-dependent relationship, with higher PASE concentrations yielding significantly better outcomes than lower concentrations. However, the effects of the low PASE concentration were not evident for some indicators. In the cellular model, the high dose of PASE suppressed high glucose (HG) stimulated renal mesangial cell proliferation, suppressed inflammatory factors and NF-κB, and decreased the levels of fibrillin-1(FN-1) and collagen IV(ColIV). CONCLUSION: Our results indicate that PS exerts favorable therapeutic effects on DKD, with the possible mechanisms including the inhibition of inflammatory pathways, suppression of mRNA levels and protein expressions of SphK1 and S1P, consequently leading to reduced overexpression of FN-1 and ColIV, thereby warranting further exploration.

A Scalable Microfluidic Platform for Nanoparticle Formulation: For Exploratory- and Industrial-Level Scales.

Nanoparticle synthesis on microfluidic platforms provides excellent reproducibility and control over bulk synthesis. While there have been plenty of platforms for producing nanoparticles (NPs) with controlled physicochemical properties, such platforms often operate in a narrow range of predefined flow rates. The flow rate limitation restricts either up-scalability for industrial production or down-scalability for exploratory research use. Here, we present a universal flow rate platform that operates over a wide range of flow rates (0.1-75 mL/min) for small-scale exploratory research and industrial-level synthesis of NPs without compromising the mixing capabilities. The wide range of flow rate is obtained by using a coaxial flow with a triangular microstructure to create a vortex regardless of the flow regime (Reynolds number). The chip synthesizes several types of NPs for gene and protein delivery, including polyplex, lipid NPs, and solid polymer NPs via self-assembly and precipitation, and successfully expresses GFP plasmid DNA in human T cells.

[Natural 5α-reductase inhibitors in treatment of benign prostatic hyperplasia].

Benign prostatic hyperplasia(BPH) is a common disease of the male urinary system, and its incidence rate in China is increasing. However, the mechanism underlying the pathogenesis of BPH remains unclear. Some studies demonstrated that the incidence of BPH was related to the change in the levels of steroid hormones. Too high content of dihydrotestosterone(DHT) in the body may cause BPH and other related diseases. Testosterone(T) is converted to DHT by 5α-reductase(SRD5A). By inhibiting the activity of this enzyme, the production of DHT can be reduced, and then the incidence of BPH can be lowered. Therefore, it has drawn great attention to screen and discover safer and more effective 5α-reductase inhibitors from natural medicines to treat prostatic hyperplasia without affecting the physiological function of men. This review summarizes the characteristics and tissue distribution of 5α-reductase, the discovery of 5α-reductase inhibitors in traditional Chinese medicine and natural medicines, 5α-reductase inhibitors commonly used in clinical practice and their side effects, as well as the animal models of prostatic hyperplasia and common detection indicators, aiming to provide a reference for more in-depth understanding and research about BPH and development of drugs.