Development of Stable and Intensified Mixing Processes for the Precise and Scalable Production of Uniform Drug Delivery Nanocarriers.

Nanocarriers show great promise in drug delivery but face challenges in stability, uniformity, and morphology control. This work introduces an enhanced mixing process to overcome these obstacles, specifically aiming to produce consistently sized poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with anti-tumor drugs. By innovatively integrating a pulsation dampener into the microfluidic channels of a continuous flow preparation system, the flow stability of piston pumps is improved nearly tenfold. Consequently, large-scale production of uniformly sized nanoparticles with customizable dimensions is achieved through nanoprecipitation. Furthermore, incorporating terminal double-bond-functionalized poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-maleimide (PLGA-PEG-Mal) enables these nanoparticles to act as nano-crosslinkers. This facilitates in situ crosslinking with thiolated hyaluronic acid via a spontaneous thiol-ene coupling reaction under physiological conditions, allowing for minimally invasive drug administration and significantly enhancing localized drug retention. The material's degradability in the presence of endogenous enzymes ensures controlled drug release, as demonstrated with the anti-tumor drug doxorubicin (DOX). Validation in a murine breast cancer model shows reduced toxicity and a substantial reduction in tumor weight compared to the free DOX group. These findings confirm the approach's effectiveness for breast cancer treatment and pave the way for innovative solutions in nanomedicine, providing a practical microfluidic mixing system for the design and large-scale production of nanomedicines.

SimpleTrackV2: Rethinking the Timing Characteristics for Multi-Object Tracking.

Multi-object tracking tasks aim to assign unique trajectory codes to targets in video frames. Most detection-based tracking methods use Kalman filtering algorithms for trajectory prediction, directly utilizing associated target features for trajectory updates. However, this approach often fails, with camera jitter and transient target loss in real-world scenarios. This paper rethinks state prediction and fusion based on target temporal features to address these issues and proposes the SimpleTrackV2 algorithm, building on the previously designed SimpleTrack. Firstly, to address the poor prediction performance of linear motion models in complex scenes, we designed a target state prediction algorithm called LSTM-MP, based on long short-term memory (LSTM). This algorithm encodes the target's historical motion information using LSTM and decodes it with a multilayer perceptron (MLP) to achieve target state prediction. Secondly, to mitigate the effect of occlusion on target state saliency, we designed a spatiotemporal attention-based target appearance feature fusion (TSA-FF) target state fusion algorithm based on the attention mechanism. TSA-FF calculates adaptive fusion coefficients to enhance target state fusion, thereby improving the accuracy of subsequent data association. To demonstrate the effectiveness of the proposed method, we compared SimpleTrackV2 with the baseline model SimpleTrack on the MOT17 dataset. We also conducted ablation experiments on TSA-FF and LSTM-MP for SimpleTrackV2, exploring the optimal number of fusion frames and the impact of different loss functions on model performance. The experimental results show that SimpleTrackV2 handles camera jitter and target occlusion better, achieving improvements of 1.6%, 3.2%, and 6.1% in MOTA, IDF1, and HOTA, respectively, compared to the SimpleTrack algorithm.

Strategies for improving loading of emulsion-based functional oil powder.

Functional oil is type of oil that is beneficial to human health and has nutritional value, however, functional oils are rich in bioactive substances such as polyunsaturated fatty acids which are sensitive to environmental factors and are susceptible to oxidation or decomposition. Construction of emulsion-based oil powder is a promising approach for improving the stability and solubility of functional oils. However, the low effective loading of oil in powder is the main challenge limiting encapsulation technology. This manuscript focuses on reviewing the current research progress of emulsion-based functional oil powder construction and systematically summarizes the processing characteristics of emulsion-based oil powder with high payload and summarizing the strategies to enhance the payload of powder in term of emulsification and drying, respectively. The impact of emulsion formation on oil powder production is discussed from different characteristics of emulsions, including emulsion composition, emulsification methods and emulsion types. In addition, the current status of improving material loading performance by various modifications to the drying technology is discussed, including the addition of drying processing additives, changes in drying parameters and the effect of innovative technological means.

Research trends in the field of retinitis pigmentosa from 2002 to 2021: a 20 years bibliometric analysis.

PURPOSE: To analyze publication trends for the past 20 years and identify potential research trends in the retinitis pigmentosa (RP) research field. METHODS: We extracted data from the Web of Science Core Collection and conducted a bibliometric analysis. All records related to RP from 2002 to 2021 were analyzed. The co-occurrence maps of keywords were generated by VOSviewer v.1.6.17 to identify knowledge structure and research trends in the RP research field. RESULTS: Totally 1976 publications from 2002 to 2021 were included in this study. The United States ranked first in the number of publications, citations and H-index. INVESTIGATIVE OPHTHALMOLOGY VISUAL SCIENCE was the most prolific journal in the RP research field. LEAGUE OF EUROPEAN RESEARCH UNIVERSITIES LERU had the greatest output in the RP research field. Tsang SH contributed to the highest number of publications in the RP research field. All keywords were divided into three clusters: (1) gene mutations, (2) pathophysiological changes, and (3) diagnosis and management in the RP research field. Average appearing years of keywords were evaluated and most of the recently appearing keywords focused on the pathophysiological changes. CONCLUSIONS: By bibliometric analysis, the knowledge structure of RP research field was identified. It may help clinicians to comprehensively understand the hotspots and guide the research trends in the RP research field.

Ultra-precise surface processing of LYSO scintillator crystals for Positron Emission Tomography.

The Lutetium-Yttrium Oxyorthosilicate (LYSO) is one of the most widely used scintillation crystal in the high-performance Positron Emission Tomography (PET) systems. The quality of the surface finish of the LYSO has an important impact on the light output, the decoding performance, the energy resolution and timing resolution of the PET detectors and systems. In this paper, we present an ultra-precise method for processing the surface of LYSO crystals. The hardness and elastic modulus of the crystals were initially measured using Nano indentation technology. The scintillators were fixed onto the plate in sparse, serried and continuous arrangements and polished using an alumina (Al2O3) and cerium oxide (CeO2) polishing solution with particles of varying size. We used a magnetorheological-polishing technique to polish the LYSO crystals. The polishing solution here included hydroxyl iron powder and hard abrasives. The hardness and elastic modulus of the crystals in question was, respectively, 11.18 ± 0.50 and 155.78 ± 4gigapascals (GPa). A 3D optical surface profiler (3D-OPS) and an atomic force microscope (AFM) were used to evaluate the quality of the polished surfaces. The average roughness of Ra 0.55 nm measured by 3D-OPS was achieved using a precise plate grinding and polishing technique. The magnetorheological-polishing method also obtained an excellent roughness of Ra 0.75 nm (3D-OPS). Our report of the use of these processing technologies can serve as a foundation for further in-depth research regarding the optimal techniques for scintillator surface processing.

Clinical Characteristics and the Prognostic Impact of Acute Kidney Injury in Critically Ill Patients with Invasive Pulmonary Aspergillosis in the Intensive Care Unit: A Retrospective, Single-Center Study.

Introduction: The incidence and impact of acute kidney injury (AKI) in patients with invasive pulmonary aspergillosis (IPA) admitted to the intensive care unit (ICU) are unknown. Methods: This retrospective study included 140 patients who were diagnosed with IPA and admitted to the medical ICU of China-Japan Friendship Hospital in Beijing, China. AKI was defined according to the Kidney Disease: Improving Global Outcomes guidelines. Data on demographic characteristics, comorbidities, laboratory tests, treatments, and prognosis at ICU admission were collected. Results: The rate of AKI was 71.4% (n = 100), and approximately 30% of the patients had preadmission acute kidney dysfunction. Of the 100 patients with AKI, 19, 8, and 73 patients had stage I, II, and III AKI, respectively, and 64 (87.6%) patients required continuous renal replacement therapy. Overall ICU mortality rate was 52.1%. Irreversible AKI was a strong independent risk factor for ICU mortality (odds ratio 13.36, 95% confidence interval 4.52-39.48, p < 0.001), followed by chronic lung disease, use of intermittent positive-pressure ventilation, and long-term corticosteroid treatment within 1 year prior to ICU admission. Higher cardiac troponin I levels at admission and worse volume control during the first 7 days of ICU stay were potential predictive factors of irreversible kidney dysfunction. Patients with irreversible AKI and those who died during the ICU stay had greater volume overload during the first 14 days of ICU stay. Patients who survived received earlier renal replacement therapy support after ICU admission compared to those who died (median, 2 vs. 5 days; p = 0.026). Conclusion: Compared to the patients with IPA in the absence of AKI, those with AKI presented with more volume overload, worse disease burden, and required stronger respiratory support, while experiencing worse prognosis. Irreversible AKI was a strong predictor of mortality in patients with critical IPA. Better volume control and earlier CRRT initiation should be considered key points in AKI management and prognostic improvement.

Constitution and reconstitution of microcapsules with high diacylglycerol oil loading capacity based on whey protein isolate / octenyl succinic anhydride starch/ inulin matrix.

The aim of this study was to constitute microcapsule systems with high oil loading capacity by octenyl succinic anhydride (OSA) starch, whey protein isolate (WPI) and inulin (IN) substrates to provide a new method for encapsulating diacylglycerol oil. Specifically, this study characterizes the physicochemical properties and reconstitution capacity of highly oil loading diacylglycerol microcapsules by comparing the wall encapsulation capacity of the binary wall system OSA-IN, WPI-IN and the ternary wall system WPI-OSA (1:9, 5:5, 9:1)-IN for diacylglycerol oil. It was found that WPI-OSA (5:5)-IN significantly improved the water solubility of microcapsules (86.11 %) compared to OSA-IN microcapsules, and the addition of WPI made the surface of microcapsules smoother and increased the thermal stability and solubility of microcapsules; the addition of OSA enhanced the wettability of microcapsules compared to WPI-IN. In addition, WPI-OSA (5:5)-IN microcapsules have the highest encapsulation efficiency (96.03 %), high emulsion stability after reconstitution, and the smallest droplet size (212.83 nm) after 28 d. Therefore, the WPI-OSA-IN composite system is suitable for the production of highly oil-loaded microencapsulated systems with excellent reconstitution ability to expand the application of diacylglycerol oil.

Inductively Coupled Plasma Dry Etching of Silicon Deep Trenches with Extremely Vertical Smooth Sidewalls Used in Micro-Optical Gyroscopes.

Micro-optical gyroscopes (MOGs) place a range of components of the fiber-optic gyroscope (FOG) onto a silicon substrate, enabling miniaturization, low cost, and batch processing. MOGs require high-precision waveguide trenches fabricated on silicon instead of the ultra-long interference ring of conventional F OGs. In our study, the Bosch process, pseudo-Bosch process, and cryogenic etching process were investigated to fabricate silicon deep trenches with vertical and smooth sidewalls. Different process parameters and mask layer materials were explored for their effect on etching. The effect of charges in the Al mask layer was found to cause undercut below the mask, which can be suppressed by selecting proper mask materials such as SiO2. Finally, ultra-long spiral trenches with a depth of 18.1 µm, a verticality of 89.23°, and an average roughness of trench sidewalls less than 3 nm were obtained using a cryogenic process at -100 °C.

Clinical characteristics and prognosis of pneumonia-related bloodstream infections in the intensive care unit: a single-center retrospective study.

Background: Bloodstream infections (BSI) are one of the most severe healthcare-associated infections in intensive care units (ICU). However, there are few studies on pneumonia-related BSI (PRBSI) in the ICU. This study aimed to investigate the clinical and prognostic characteristics of patients with PRBSI in the ICU and to provide a clinical basis for early clinical identification. Methods: We retrospectively collected data from patients with bacterial BSI in a single-center ICU between January 1, 2017, and August 31, 2020. Clinical diagnosis combined with whole-genome sequencing (WGS) was used to clarify the diagnosis of PRBSI, and patients with PRBSI and non-PRBSI were analyzed for clinical features, prognosis, imaging presentation, and distribution of pathogenic microorganisms. Results: Of the 2,240 patients admitted to the MICU, 120 with bacterial BSI were included in this study. Thirty-two (26.7%) patients were identified as having PRBSI based on the clinical diagnosis combined with WGS. Compared to patients without PRBSI, those with PRBSI had higher 28-day mortality (81.3 vs.51.1%, p = 0.003), a higher total mortality rate (93.8 vs. 64.8%, p = 0.002), longer duration of invasive mechanical ventilation (median 16 vs. 6 days, p = 0.037), and prolonged duration of ICU stay (median 21 vs. 10 days, p = 0.004). There were no differences in other baseline data between the two groups, but patients with PRBSI had extensive consolidation on chest radiographs and significantly higher Radiographic Assessment of Lung Edema scores (mean 35 vs. 24, p < 0.001). The most common causative organisms isolated in the PRBSI group were gram-negative bacteria (n = 31, 96.9%), with carbapenem-resistant gram-negative bacteria accounting for 68.8% (n = 22) and multidrug-resistant bacteria accounting for 81.3% (n = 26). Conclusion: Pneumonia-related BSI is an important component of ICU-BSI and has a poor prognosis. Compared to non-PRBSI, patients with PRBSI do not have typical clinical features but have more severe lung consolidation lesions, and should be alerted to the possibility of their occurrence when combined with pulmonary gram-negative bacterial infections, especially carbapenem-resistant bacteria. Further multicenter, large-sample studies are needed to identify the risk factors for the development of PRBSI and prevention and treatment strategies.

A New Prognostic Index PDPI for the Risk of Pneumonia Among Patients With Diabetes.

Objective: Risk factors for the development of pneumonia among patients with diabetes mellitus are unclear. The aim of our study was to elucidate the potential risk factors and attempt to predict the probability of pneumonia based on the history of diabetes. Methods: We performed a population-based, prospective multicenter cohort study of 1,043 adult patients with diabetes in China during 2017-2019. Demographic information, comorbidities, or laboratory examinations were collected. Results: The study included 417 diabetic patients with pneumonia and 626 no-pneumonia-onset diabetic patients. The predictive risk factors were chosen on the basis of a multivariate logistic regression model to predict pneumonia among patients with diabetes including male sex [odds ratio (OR) = 1.72, 95% confidence interval (CI): 1.27-2.33, p < 0.001], age ≥ 75 years (OR = 2.31, 95% CI: 1.61-3.31, p < 0.001), body mass index < 25 (OR = 2.59, 95% CI: 1.92-3.50, p < 0.001), chronic obstructive pulmonary disease (OR = 6.58, 95% CI: 2.09-20.7, p = 0.001), hypertension (OR = 4.27, 95% CI: 3.12-5.85, p < 0.001), coronary heart disease (OR = 2.98, 95% CI: 1.61-5.52, p < 0.001), renal failure (OR = 1.82, 95% CI: 1.002-3.29, p = 0.049), cancer (OR = 3.57, 95% CI: 1.80-7.06, p < 0.001), use of insulin (OR = 2.28, 95% CI: 1.60-3.25, p < 0.001), and hemoglobin A1c ≥ 9% (OR = 2.70, 95% CI: 1.89-3.85, p < 0.001). A predictive nomogram was established. This model showed c-statistics of 0.811, and sensitivity and specificity were 0.717 and 0.780, respectively, under cut-off of 125 score. Conclusion: We designed a clinically predictive tool for assessing the risk of pneumonia among adult patients with diabetes. This tool stratifies patients into relevant risk categories and may provide a basis for individually tailored intervention for the purpose of early prevention.

Increased Antimicrobial Resistance among Sputum Pathogens from Patients with Hyperglycemia.

BACKGROUND: Glucose management is of great significance. Infection and hyperglycemia are a vicious circle. This study was conducted to describe distribution and antimicrobial resistance of bacteria isolated from patients with normoglycemia, hyperglycemia, or diabetes on admission. METHODS: A retrospective study was conducted in a teaching hospital from January 2015 to March 2017. Bacteria were identified by the Vitek 2 automated system and antimicrobial susceptibility determined. RESULTS: A total of 1,163 patients were included: 582 with normoglycemia, 292 with hyperglycemia and 289 with diabetes. Enterobacter, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterococcus faecium were the main species isolated from these patients, with 1,616 unduplicated isolates from sputum samples. Patients with hyperglycemia were more prone to carry more than one species, and the rate of multidrug-resistant K. pneumoniae and methicillin-resistant S. aureus was higher in this group. K. pneumoniae from hyperglycemia patients demonstrated increased resistance to carbapenems, especially imipenem (p=0.002) and meropenem (p=0.003), than those isolated from patients with normoglycemia or diabetes. No significance was detected for K. pneumoniae, A. baumannii, or P. aeruginosa between nondiabetes and diabetes patients. In addition, hyperglycemia patients had a higher rate of ICU admission (p=0.035) and a lower survival rate (p<0.001). CONCLUSION: Patients with hyperglycemia were more prone to carry bacteria, especially multidrug-resistant K. pneumoniae and methicillin-resistant S. aureus. Assessing glucose on admission is of great significance in predicting bacterial carriage and antimicrobial resistance.

Exploring microbial dynamics associated with flavours production during highland barley wine fermentation.

Highland barley wine (HBW) is a well-known grain wine in Qinghai-Tibet Plateau, China and is mainly fermented by local Qu (a traditional starter) with highland barley (Hordeum vulgare, Qingke (Tibetan hulless barley)), and the flavors profiles associated with microbiota succession during HBW fermentation are unrevealed. Hence, high-throughput sequencing (HTS) technology was used to investigate the dynamic changes of microbial community for the duration of the fermentation. In addition, metabolites were analyzed by gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC). A total of 66 volatile compounds and 7 organic acids were identified during the traditional brewing process. Results showed that the composition of microbiota varied over the fermentation process. The bacterial genera (relative abundance > 0.1%) decreased from 13 at 0 h to 4 encompassing Leuconostoc (13.53%) and Acetobacter (74.60%) after 48 h fermentation, whilst the structure of fungal community was more uniform in comparison with bacteria, as Rhizopus and Saccharomyces were predominant throughout the fermentation. Furthermore, the correlations between microbiota and the detected compounds were also explored, which highlighted that three bacterial genera, including Acetobacter, Leuconostoc, Bacillus and one fungal genus Rhizopus were significantly correlated with main flavours compounds (|r| > 0.7, FDR < 0.01). To conclude, the detailed information provided by this study offer screening strategies of beneficial bacterial and fungal strains to improve the quality of HBW.

The mNCP-SPI Score Predicting Risk of Severe COVID-19 among Mild-Pneumonia Patients on Admission.

PURPOSE: To predict the risk of developing severe pneumonia among mild novel coronavirus pneumonia (mNCP) patients on admission. METHODS: A retrospective cohort study was conducted at three hospitals in Shanghai and Wuhan from January 2020 to February 2020. Real-time polymerasechain-reaction assays were used to detect COVID-19. A total of 529 patients diagnosed with NCP were recruited from three hospitals and classified by four severity types during hospitalization following the standards of the Chinese Diagnosis and Treatment of Pneumonia Caused by New Coronavirus Infection (eighth version). Patients were excluded if admitted by ICU on admission (n=92, on a general ward while meeting the condition of severe or critical type on admission (n=25), or there was insufficient clinical information (n=64). In sum, 348 patients with mNCP were finally included, and 68 developed severe pneumonia. RESULTS: mNCP severity prognostic index values were calculated based on multivariate logistic regression: history of diabetes (OR 2.064, 95% CI 1.010-4.683; p=0.043), time from symptom onset to admission ≥7 days (OR 1.945, 95% CI 1.054-3.587; p=0.033), lymphocyte count ≤0.8 (OR 1.816, 95% CI 1.008-3.274; p=0.047), myoglobin ≥90 mg/L (OR 2.496, 95% CI 1.235-5.047; p=0.011), and D-dimer ≥0.5 mg/L (OR 2.740, 95% CI 1.395-5.380; p=0.003). This model showed a c-statistics of 0.747, with sensitivity and specificity 0.764 and 0.644, respectively, under cutoff of 165. CONCLUSION: We designed a clinical predictive tool for risk of severe pneumonia among mNCP patients to provided guidance for medicines. Further studies are required for external validation.

Clinical Features Predicting Mortality Risk in Patients With Viral Pneumonia: The MuLBSTA Score.

OBJECTIVE: The aim of this study was to further clarify clinical characteristics and predict mortality risk among patients with viral pneumonia. METHODS: A total of 528 patients with viral pneumonia at RuiJin hospital in Shanghai from May 2015 to May 2019 were recruited. Multiplex real-time RT-PCR was used to detect respiratory viruses. Demographic information, comorbidities, routine laboratory examinations, immunological indexes, etiological detections, radiological images and treatment were collected on admission. RESULTS: 76 (14.4%) patients died within 90 days in hospital. A predictive MuLBSTA score was calculated on the basis of a multivariate logistic regression model in order to predict mortality with a weighted score that included multilobular infiltrates (OR = 5.20, 95% CI 1.41-12.52, p = 0.010; 5 points), lymphocyte ≤ 0.8∗109/L (OR = 4.53, 95% CI 2.55-8.05, p < 0.001; 4 points), bacterial coinfection (OR = 3.71, 95% CI 2.11-6.51, p < 0.001; 4 points), acute-smoker (OR = 3.19, 95% CI 1.34-6.26, p = 0.001; 3 points), quit-smoker (OR = 2.18, 95% CI 0.99-4.82, p = 0.054; 2 points), hypertension (OR = 2.39, 95% CI 1.55-4.26, p = 0.003; 2 points) and age ≥60 years (OR = 2.14, 95% CI 1.04-4.39, p = 0.038; 2 points). 12 points was used as a cut-off value for mortality risk stratification. This model showed sensitivity of 0.776, specificity of 0.778 and a better predictive ability than CURB-65 (AUROC = 0.773 vs. 0.717, p < 0.001). CONCLUSION: Here, we designed an easy-to-use clinically predictive tool for assessing 90-day mortality risk of viral pneumonia. It can accurately stratify hospitalized patients with viral pneumonia into relevant risk categories and could provide guidance to make further clinical decisions.