Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 1.004
1.
J Vis Exp ; (207)2024 May 03.
Article En | MEDLINE | ID: mdl-38767369

A total of five samples of Chrysomya megacephala samples - three fresh samples, one sample stored in alcohol for 2 years, and one sample stored in dry sealed storage for 2 years protected from light only - were selected to investigate whether a blood DNA extraction kit could extract DNA from necrophilous flies and to determine whether alcohol could prolong the preservation of necrophilous flies' DNA. First, the blood DNA extraction kit was used to extract DNA from their thorax tissues. Then, the DNA purity and concentration were examined using a microplate reader and a fluorometer. Finally, PCR amplification and electrophoresis of the extracted DNA were done with necrophilic fly-specific primers located in the mitochondrial CO I gene sequence. The results showed that the DNA purity of all samples was greater than 2.0. The DNA concentration was observed to be of the following order: fresh samples > alcohol-preserved old samples > untreated, old samples. All samples had specific electrophoretic bands after PCR amplification. In conclusion, a blood DNA extraction kit can be used to extract DNA from necrophilic flies successfully, and the DNA concentration of fresh fly samples is greater than that of old fly samples. The flies can be stored in alcohol for a long time.


DNA , Polymerase Chain Reaction , Animals , DNA/isolation & purification , DNA/genetics , Polymerase Chain Reaction/methods , Calliphoridae/genetics , Calliphoridae/chemistry
2.
Front Endocrinol (Lausanne) ; 15: 1354614, 2024.
Article En | MEDLINE | ID: mdl-38800470

Background: The coexistence of heart failure and diabetes is prevalent, particularly in Intensive Care Units (ICU). However, the relationship between the triglyceride-glucose (TyG) index, heart failure, diabetes, and the length of hospital stay (LHS) in patients with cerebrovascular disease in the ICU remains uncertain. This study aims to investigate the association between the TyG index and LHS in patients with heart failure and diabetes. Methods: This retrospective study utilized the Medical Information Mart for Intensive Care (MIMIC)-IV database to analyze patients with diabetes and heart failure. Participants were categorized into quartiles based on the TyG index, and the primary outcome was LHS. The association between the TyG index at ICU admission and LHS was examined through multivariable logistic regression models, restricted cubic spline regression, and subgroup analysis. Results: The study included 635 patients with concurrent diabetes and heart failure. The fully adjusted model demonstrated a positive association between the TyG index and LHS. As a tertile variable (Q2 and Q3 vs Q1), the beta (ß) values were 0.88 and 2.04, with a 95% confidence interval (95%CI) of -0.68 to 2.44 and 0.33 to 3.74, respectively. As a continuous variable, per 1 unit increment, the ß (95% CI) was 1.13 (0.18 to 2.08). The TyG index's relationship with LHS showed linearity (non-linear p = 0.751). Stratified analyses further confirmed the robustness of this correlation. Conclusion: The TyG index exhibited a linearly positive association with the LHS in patients with both heart failure and diabetes. Nevertheless, prospective, randomized, controlled studies are imperative to substantiate and validate the findings presented in this investigation.


Blood Glucose , Diabetes Mellitus, Type 2 , Heart Failure , Intensive Care Units , Length of Stay , Triglycerides , Humans , Heart Failure/blood , Heart Failure/epidemiology , Female , Male , Retrospective Studies , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Intensive Care Units/statistics & numerical data , Triglycerides/blood , Aged , Length of Stay/statistics & numerical data , Blood Glucose/analysis , Blood Glucose/metabolism , Middle Aged , Aged, 80 and over
3.
Plants (Basel) ; 13(10)2024 May 17.
Article En | MEDLINE | ID: mdl-38794472

(1) Background: Crop yields in China's arid and semi-arid regions are limited by water shortages. Exploring the interactions and resource utilization among agroforestry species is key to maintaining diversified agricultural production. (2) Objective: An apple-watermelon agroforestry system and watermelon sole-cropping system were compared to quantify how resource availability (light, water) and watermelon performance (leaf photosynthetic rate, growth, and yield) change with irrigation strategies. (3) Methods: A three-year apple and watermelon field experiment was conducted in a young apple orchard in the arid area of central Ningxia to test the effect of light competition and irrigation systems on light environment, leaf photosynthetic rate, plant growth, and yield in watermelon. The experiment encompassed two planting patterns: (i) apple-watermelon agroforestry (AF) and watermelon sole-cropping (SC) and (ii) three irrigation quotas (W1: 105 mm, W2: 210 mm, and W3: 315 mm). (4) Results: The results show that the agroforestry planting pattern extended the growth period of watermelon and increased the leaf area index. Mean daily shade intensity increased by 16.02% from 2020 to 2022. The land equivalent ratio (LER) was >1 in 2021 and 2022. The SWC, leaf photosynthetic rate, LAI, and yield of watermelon in an agroforestry planting pattern were lower than when in a sole-cropping planting pattern. However, under the W1 irrigation strategy, the total soluble solids of the agroforestry planting pattern were 2.27% higher than those of the sole-cropping pattern, and the yield of the agroforestry planting pattern was 2.59% higher than that of the sole-cropping pattern. Under the W3 irrigation strategy, the average watermelon weight in the agroforestry planting pattern was 2.85% higher than that of the sole-cropping pattern. A path analysis showed that the agroforestry planting pattern can increase the yield by increasing soil water content, which is different from the sole-cropping pattern. (5) Conclusions: The results confirm that the apple-watermelon agroforestry planting pattern reduced watermelon yields. However, the LER of the agroforestry system was greater than 1.0. It is reasonable to plant watermelons in young apple forests.

4.
Cureus ; 16(3): e55885, 2024 Mar.
Article En | MEDLINE | ID: mdl-38595883

Recurrence of a lung tumor invading the subclavian artery, causing stenosis and leading to finger ulcers as the initial symptom, is rare. We employed endovascular techniques, inserting a Viabahn® VBX covered stent (W. L. Gore & Associates, Flagstaff, Arizona) to aid in ulcer healing and improve the patient's quality of life. The patient, a 73-year-old male, had a history of lung adenocarcinoma resection two years prior but had not undergone follow-up examinations or cancer-specific treatments. Clinical examination revealed an invasion of the right subclavian artery by the recurrent tumor, resulting in severe stenosis and ischemic symptoms in the right upper limb. Given the patient's advanced cancer stage and the decline of further tumor-specific treatments, an endovascular intervention using a Viabahn VBX covered stent was performed to improve blood flow and promote ulcer healing. The stent demonstrated exceptional stability and patency during the six-month follow-up, greatly improving the patient's quality of life. This case highlights the importance of recognizing atypical symptoms as potential indicators of tumor recurrence or progression and demonstrates the promising role of covered stents in managing vascular complications in selected patients with advanced-stage malignancies.

5.
Mol Ther ; 2024 Apr 06.
Article En | MEDLINE | ID: mdl-38582962

Cellular senescence associates with pathological aging and tissue dysfunctions. Studies utilizing mouse models for cell lineage tracings have emphasized the importance of senescence heterogeneity in different organs and cell types. Here, we constructed a p21- (Akaluc - tdTomato - Diphtheria Toxin Receptor [DTR]) (ATD) mouse model to specifically study the undefined mechanism for p21-expressing senescent cells in the aged and liver injury animals. The successful expressions of these genes enabled in vitro flow cytometric sorting, in vivo tracing, and elimination of p21-expressing senescent cells. During the natural aging process, p21-expressing cells were found in various tissues of p21-ATD mice. Eliminating p21-expressing cells in the aged p21-ATD mice recovered their multiple biological functions. p21-ATD/Fah-/- mice, bred from p21-ATD mice and fumarylacetoacetate hydrolase (Fah)-/- mice of liver injury, showed that the majority of their senescent hepatocytes were the phenotype of p21+ rather than p16+. Furthermore, eliminating the p21-expressing hepatocytes significantly promoted the engraftment of grafted hepatocytes and facilitated liver repopulation, resulting in significant recovery from liver injury. Our p21-ATD mouse model serves as an optimal model for studying the pattern and function of p21-expressing senescent cells under the physical and pathological conditions during aging.

6.
Environ Microbiol Rep ; 16(2): e13250, 2024 Apr.
Article En | MEDLINE | ID: mdl-38575119

The rhizosphere and phyllosphere of plants are home to a diverse range of microorganisms that play pivotal roles in ecosystem services. Consequently, plant growth-promoting bacteria (PGPB) are extensively utilized as inoculants to enhance plant growth and boost productivity. Despite this, the interactions between the rhizosphere and phyllosphere, which are influenced by PGPB inoculation, have not been thoroughly studied to date. In this study, we inoculated Bacillus velezensis SQR9, a PGPB, into the bulk soil, rhizosphere or phyllosphere, and subsequently examined the bacterial communities in the rhizosphere and phyllosphere using amplicon sequencing. Our results revealed that PGPB inoculation increased its abundance in the corresponding compartment, and all treatments demonstrated plant growth promotion effects. Further analysis of the sequencing data indicated that the presence of PGPB exerted a more significant impact on bacterial communities in both the rhizosphere and phyllosphere than in the inoculation compartment. Notably, the PGPB stimulated similar rhizosphere-beneficial microbes regardless of the inoculation site. We, therefore, conclude that PGPB can promote plant growth both directly and indirectly through the interaction between the rhizosphere and phyllosphere, leading to the enrichment of beneficial microorganisms.


Bacillus , Ecosystem , Rhizosphere , Plant Roots/microbiology , Bacteria/genetics , Soil Microbiology
7.
Front Public Health ; 12: 1368744, 2024.
Article En | MEDLINE | ID: mdl-38435292

Background: In May-June 2023, an unprecedented outbreak of human respiratory syncytial virus (HRSV) infections occurred in a kindergarten, Zhejiang Province, China. National, provincial, and local public health officials investigated the cause of the outbreak and instituted actions to control its spread. Methods: We interviewed patients with the respiratory symptoms by questionnaire. Respiratory samples were screened for six respiratory pathogens by real-time quantitative polymerase chain reaction (RT-PCR). The confirmed cases were further sequenced of G gene to confirm the HRSV genotype. A phylogenetic tree was reconstructed by maximum likelihood method. Results: Of the 103 children in the kindergarten, 45 were classified as suspected cases, and 25 cases were confirmed by RT-PCR. All confirmed cases were identified from half of classes. 36% (9/25) were admitted to hospital, none died. The attack rate was 53.19%. The median ages of suspected and confirmed cases were 32.7 months and 35.8 months, respectively. Nine of 27 confirmed cases lived in one community. Only two-family clusters among 88 household contacts were HRSV positive. A total of 18 of the G gene were obtained from the confirmed cases. Phylogenetic analyses revealed that 16 of the sequences belonged to the HRSV B/BA9 genotype, and the other 2 sequences belonged to the HRSV A/ON1 genotype. The school were closed on June 9 and the outbreak ended on June 15. Conclusion: These findings suggest the need for an increased awareness of HRSV coinfections outbreak in the kindergarten, when HRSV resurges in the community after COVID-19 pandemic.


Respiratory Syncytial Virus, Human , Child , Humans , Child, Preschool , Respiratory Syncytial Virus, Human/genetics , Pandemics , Phylogeny , Schools , Disease Outbreaks , China/epidemiology
8.
Heliyon ; 10(5): e27318, 2024 Mar 15.
Article En | MEDLINE | ID: mdl-38486767

Existing methods of measuring energy consumption require complex statistics and computing. A real-time and globally applicable approach for comparing energy consumption across different cities is still lacking. Additionally, the nonlinear relationships and varying thresholds of energy consumption in relation to economic activities and urbanization remain unconfirmed. This study aims to fill these gaps by utilizing Suomi National Polar-orbiting Partnership Visible Infrared Imaging Radiometer Suite (NPP-VIIRS) nighttime light data in 2015 and a top-down approach based on a multiple regression model to examine energy consumption in global cities employing a redefined urban boundary. It also explores the accurate relationship between energy consumption, population density (as a proxy of urbanization), and per capita gross domestic product (GDP) across different regions and urban sizes using generalized additive models and regression models. High-resolution gridded population and GDP datasets covering the entire planet are utilized for this purpose. The study also estimates the development potentiality. The study yields followings outcomes: Firstly, the top 30 cities with the highest per capita energy consumption account for over 0.66% of the total per capita energy consumption of all cities. Secondly, in East Asia (EA) and Southeast Asia (SEA), the per capita energy consumption decreases when per capita GDP reaches $40,000 and $75,000, respectively, while it remains stable in cities located in Western Europe (WE) and North America (NA) as per capita GDP increases. Thirdly, the per capita energy consumption declines with increasing urban population density until reaching 10,000 person/km2, 22,000 person/km2, and 4000 person/km2 in EA, SEA, and NA, respectively. Fourthly, in Central Asia (CA), megacities can save over 100 Mbtu/population when per capita GDP increases by $1000 compared to big cities. This pioneering study provides a comparable investigation of energy consumption at the global city level, exploring its relationship with urbanization and economy by employing a unified calculation standard. It will facilitate long-term energy-saving policies and urban planning strategies.

9.
World J Gastrointest Oncol ; 16(2): 259-272, 2024 Feb 15.
Article En | MEDLINE | ID: mdl-38425391

Approximately 20% of colorectal cancer (CRC) patients present with metastasis at diagnosis. Among Stage I-III CRC patients who undergo surgical resection, 18% typically suffer from distal metastasis within the first three years following initial treatment. The median survival duration after the diagnosis of metastatic CRC (mCRC) is only 9 mo. mCRC is traditionally considered to be an advanced stage malignancy or is thought to be caused by incomplete resection of tumor tissue, allowing cancer cells to spread from primary to distant organs; however, increasing evidence suggests that the mCRC process can begin early in tumor development. CRC patients present with high heterogeneity and diverse cancer phenotypes that are classified on the basis of molecular and morphological alterations. Different genomic and nongenomic events can induce subclone diversity, which leads to cancer and metastasis. Throughout the course of mCRC, metastatic cascades are associated with invasive cancer cell migration through the circulatory system, extravasation, distal seeding, dormancy, and reactivation, with each step requiring specific molecular functions. However, cancer cells presenting neoantigens can be recognized and eliminated by the immune system. In this review, we explain the biological factors that drive CRC metastasis, namely, genomic instability, epigenetic instability, the metastatic cascade, the cancer-immunity cycle, and external lifestyle factors. Despite remarkable progress in CRC research, the role of molecular classification in therapeutic intervention remains unclear. This review shows the driving factors of mCRC which may help in identifying potential candidate biomarkers that can improve the diagnosis and early detection of mCRC cases.

10.
Hum Fertil (Camb) ; 27(1): 2316005, 2024 Dec.
Article En | MEDLINE | ID: mdl-38357937

This study aimed to evaluate the cumulative live birth rate (cLBR) of progestin-primed ovarian stimulation (PPOS) protocol versus gonadotropin-releasing hormone antagonist (GnRH-ant) protocol for in vitro fertilization (IVF) cycle in infertile women with normal ovarian reserve (NOR). Infertile women with NOR who underwent their first IVF cycle were enrolled in an open-label randomized controlled trial. Patients were randomly assigned 1:1 to receive a freeze-all strategy with delayed embryo transfer (PPOS group, n = 174) and fresh embryo transfer first (GnRH-ant group, n = 174). The primary outcome was the cLBR per aspiration. The cLBR between the PPOS group and GnRH-ant group were comparable (55.75% vs. 52.87%, p = 0.591). A premature luteinizing hormone surge was not observed in the PPOS group, while there were six cases (3.45%) in the GnRH-ant group, but no premature ovulation in either of the groups. The pregnancy outcomes, including implantation rate, clinical pregnancy rate and miscarriage rate, were all comparable. In addition, the number of retrieved oocytes, mature oocytes and viable embryos were similar (all p > 0.05) between the two groups.


Infertility, Female , Ovarian Reserve , Pregnancy , Female , Humans , Progestins/therapeutic use , Infertility, Female/therapy , Birth Rate , Gonadotropin-Releasing Hormone , Fertilization in Vitro/methods , Ovulation Induction/methods , Pregnancy Rate , Hormone Antagonists/therapeutic use , Retrospective Studies , Randomized Controlled Trials as Topic
11.
Nature ; 626(7998): 288-293, 2024 Feb.
Article En | MEDLINE | ID: mdl-38326594

The microscopic origin of high-temperature superconductivity in cuprates remains unknown. It is widely believed that substantial progress could be achieved by better understanding of the pseudogap phase, a normal non-superconducting state of cuprates1,2. In particular, a central issue is whether the pseudogap could originate from strong pairing fluctuations3. Unitary Fermi gases4,5, in which the pseudogap-if it exists-necessarily arises from many-body pairing, offer ideal quantum simulators to address this question. Here we report the observation of a pair-fluctuation-driven pseudogap in homogeneous unitary Fermi gases of lithium-6 atoms, by precisely measuring the fermion spectral function through momentum-resolved microwave spectroscopy and without spurious effects from final-state interactions. The temperature dependence of the pairing gap, inverse pair lifetime and single-particle scattering rate are quantitatively determined by analysing the spectra. We find a large pseudogap above the superfluid transition temperature. The inverse pair lifetime exhibits a thermally activated exponential behaviour, uncovering the microscopic virtual pair breaking and recombination mechanism. The obtained large, temperature-independent single-particle scattering rate is comparable with that set by the Planckian limit6. Our findings quantitatively characterize the pseudogap in strongly interacting Fermi gases and they lend support for the role of preformed pairing as a precursor to superfluidity.

12.
Anal Bioanal Chem ; 416(4): 873-882, 2024 Feb.
Article En | MEDLINE | ID: mdl-38062196

This study presents a novel approach for the quantification of silver ions in environmental water through the utilization of liquid-liquid microextraction, employing natural deep eutectic solvents in conjunction with inductively coupled plasma emission spectroscopy. The extracted solvent was characterized by Fourier transform infrared spectroscopy (FT-IR). The impact of various extractant types, extractant molar ratio, extractant volume, extraction time, and salt concentration on the efficacy of silver ion extraction was investigated. The findings indicate that the optimal extraction efficiency was attained by utilizing a 5-mL aqueous solution volume, containing 1000 µL thymol/lactic acid NADES 1:3, a salt concentration of 1 mg mL-1, a pH value of 4, and a vortex time of 4 min. Upon implementing the optimized experimental conditions, the recovery of target metal ions was from 96.9 to 101.0%. The relative standard deviations were observed to be within the range of 1.5 to 2.7%. The present study demonstrates the reproducibility, accuracy, and reliability of the method for detecting silver ions in environmental water, with linear range of 5~1000 ng mL-1 and limits of detection (LOD) and limits of quantification (LOQ) of 1.52 ng mL-1 and 5.02 ng mL-1, respectively.

13.
Eur J Clin Microbiol Infect Dis ; 43(1): 139-153, 2024 Jan.
Article En | MEDLINE | ID: mdl-37985551

PURPOSE: The extensive use of vancomycin has led to the development of Staphylococcus aureus strains with varying degrees of resistance to vancomycin. The present study aimed to explore the molecular causes of vancomycin resistance by conducting a proteomics analysis of subcellular fractions isolated from vancomycin-intermediate resistant S. aureus (VISA) and vancomycin-sensitive S. aureus (VSSA) strains. METHODS: We conducted proteomics analysis of subcellular fractions isolated from 2 isogenic S. aureus strains: strain 11 (VSSA) and strain 11Y (VISA). We used an integrated quantitative proteomics approach assisted by bioinformatics analysis, and comprehensively investigated the proteome profile. Intensive bioinformatics analysis, including protein annotation, functional classification, functional enrichment, and functional enrichment-based cluster analysis, was used to annotate quantifiable targets. RESULTS: We identified 128 upregulated proteins and 21 downregulated proteins in strain 11Y as compared to strain 11. The largest group of differentially expressed proteins was composed of enzymatic proteins associated with metabolic and catalytic activity, which accounted for 32.1% and 50% of the total proteins, respectively. Some proteins were indispensable parts of the regulatory networks of S. aureus that were altered with vancomycin treatment, and these proteins were related to cell wall metabolism, cell adhesion, proteolysis, and pressure response. CONCLUSION: Our proteomics study revealed regulatory proteins associated with vancomycin resistance in S. aureus. Some of these proteins were involved in the regulation of cell metabolism and function, which provides potential targets for the development of strategies to manage vancomycin resistance in S. aureus.


Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Humans , Staphylococcus aureus/genetics , Vancomycin/pharmacology , Vancomycin/therapeutic use , Proteomics , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Microbial Sensitivity Tests
14.
Altern Ther Health Med ; 30(2): 124-130, 2024 Feb.
Article En | MEDLINE | ID: mdl-37856802

Objective: The primary objectives of this study were to compare the characteristics of older and younger patients with sepsis and to analyze risk factors associated with 28-day and 90-day mortality in critically ill patients. Our study aimed to explore whether there are significant differences between sepsis patients in different age groups and whether these differences are related to the association between disease severity and mortality. Methods: We conducted a single-center, retrospective study of 5783 critically ill patients over 18 years of age from the Medical Information Mart for Intensive Care III database diagnosed with sepsis and admitted to the intensive care unit between 2008 and 2012. We performed a retrospective analysis, selected the Critical Care Medicine Information Mart III database, and collected data on patients with sepsis. We then collated and analyzed these data to compare differences in characteristics between older and younger patients and identify associated risk factors, which can help understand patient mortality. This approach leverages existing clinical data and avoids new experiments or data collection. Kaplan-Meier survival curve was used to assess 28-day and 90-day mortality, and a Cox proportional hazards regression model was used to evaluate the associated risk factors with 28-day and 90-day mortality. Results: Our study identified significant differences in mortality between older and younger patients with sepsis, finding that older patients had significantly higher mortality than younger patients. Furthermore, we successfully identified risk factors associated with mortality, results that have important implications for optimizing patient care and making clinical decisions. Of 5783 patients with sepsis, 2044 (35.3%) were younger than 60 years, and 3739 (64.7%) were aged 60 years or older. The 28-day mortality rate was 11.8% and 21.2% in the younger and older cohorts, respectively (P < .01). In the age-stratified analysis, the 28-day mortality was the highest in patients aged over 80 years (14.6% vs. 21.2% vs. 26.8%, P < .001). Factors associated with 28-day and 90-day mortality in patients with sepsis included age, weight, the need for mechanical ventilation, congestive heart failure, chronic pulmonary disease, malignancy, and Sequential Organ Failure Assessment score. Higher mortality in older patients with sepsis suggests the need for more aggressive treatment and monitoring. We also identified risk factors associated with mortality, helping to develop individualized treatment strategies. In addition, the different clinical characteristics of patients in different age groups emphasize the need for refined care pathways to meet their special needs. These results will help improve the treatment effect and quality of life of patients with sepsis. Conclusions: Our study fills the knowledge gap on the manifestations of sepsis patients in different age groups and helps medical staff better predict and manage disease progression in these two groups and provide personalized treatment. This lays the foundation for future in-depth research on age-related sepsis factors and is expected to improve patient survival and recovery rates. Older patients with sepsis had higher mortality rates and adverse outcomes. The mortality rate in patients with sepsis gradually increased with age. The importance of these findings is that they can help guide patient care and clinical decision-making, particularly when dealing with older and younger patients with sepsis, to improve treatment outcomes and reduce mortality. We would like to acknowledge that there are several limitations to the study, including the selectivity of the database and the retrospective nature, which preclude inference of causal relationships. In addition, some unconsidered variables may affect the results, and missing information in the data may also have an impact on the study. Future research could further explore these issues.This study highlights the critical role of age in sepsis patient outcomes and provides a strong basis for more sophisticated care and treatment. Our findings will help save more lives and improve patients' chances of recovery, which has profound implications for future research and clinical practice in the field of sepsis.


Critical Illness , Sepsis , Humans , Adolescent , Adult , Aged, 80 and over , Aged , Retrospective Studies , Quality of Life , Intensive Care Units , Sepsis/therapy , Sepsis/diagnosis
15.
Biotechnol Prog ; 40(1): e3389, 2024.
Article En | MEDLINE | ID: mdl-37747847

Tangential flow filtration (TFF) through a 30 kDa nominal molecular weight cut-off (MWCO) ultrafiltration membrane is widely employed to concentrate purified monoclonal antibodies (mAbs) to levels required for their formulation into injectable biologics. While TFF has been used to remove casein from milk for cheese production for over 35 years, and in pharmaceutical manufacture of biotherapeutic proteins for 20 years, the rapid decline in filtration rate (i.e., flux) at high protein concentrations is a limitation that still needs to be addressed. This is particularly important for mAbs, many of which are 140-160 kDa immunoglobulin G (IgG) type proteins recovered at concentrations of 200 mg/mL or higher. This work reports the direct measurement of local transmembrane pressure drops and off-line confocal imaging of protein accumulation in stagnant regions on the surface of a 30 kDa regenerated cellulose membrane in a flat-sheet configuration widely used in manufacture of biotherapeutic proteins. These first-of-a-kind measurements using 150 kDa bovine IgG show that while axial pressure decreases by 58 psi across a process membrane cassette, the decrease in transmembrane pressure drop is constant at about 1.2 psi/cm along the 20.7 cm length of the membrane. Confocal laser scanning microscopy of the membrane surface at the completion of runs where retentate protein concentration exceeds 200 mg/mL, shows a 50 µm thick protein layer is uniformly deposited. The localized measurements made possible by the modified membrane system confirm the role of protein deposition on limiting ultrafiltration rate and indicate possible targets for improving membrane performance.


Filtration , Ultrafiltration , Animals , Cattle , Filtration/methods , Ultrafiltration/methods , Milk , Antibodies, Monoclonal/metabolism , Membranes, Artificial , Immunoglobulin G
16.
Chinese Pharmacological Bulletin ; (12): 381-389, 2024.
Article Zh | WPRIM | ID: wpr-1013622

Aim To discover the potential active compounds and possible mechanisms in rheumatoid arthritis (RA) treatment with Zhi-Huang-Zhi-Tong powder (ZHZTP) by using network pharmacology and in vitro study. Methods The active ingredient targets and disease targets of Zhihuang Zhitong Powder were searched and screened by database; they intersected to get a common target; and the "drug-component-target" relationship network diagram was constructed for GO and KEGG enrichment analysis of the overlapping genes; then the core components were docked with the core targets. Finally, based on the inflammation model of HUVECs in vitro, the efficacy and mechanism of Zhihuang Zhitong powder were verified by MTT method, plate scratch test and Western blot. Results Active compounds involved in RA treatment were screened in the present study, and the top two were ursolic acid and emodin, all playing crucial roles in RA treatment with ZHZTP. Additionally, the key target was AKTA, TNF and IL-6. GO and KEGG enrichment analysis revealed that ZHZTP regulated BP, MF and CC, and also focused on regulating AKTA, TNF and IL-6 signaling pathway. Molecular docking showed that interactions between key active compounds and key targets were stable. In vitro ZHZTP significantly inhibited cell viability and migration of TNF-a-stimulated HUVECs, and the involved mechanism may be associated with PI3K/AKT/m-TOR signaling. Conclusions The present study reveals that the potential active compounds of ZHZTP are ursolic acid and emodin, and moreover, the involved mechanisms of ZHZTP for RA treatment are associated with PI3 K/AKT/m-TOR signaling.

17.
Article Zh | WPRIM | ID: wpr-1012302

Objective: To investigate the clinical characteristics of induced labor in twin pregnancy and the related factors of induced labor failure. Methods: The clinical data of twin pregnant women who underwent induced labor in Peking University Third Hospital from January 2016 to December 2022 were retrospectively analyzed. According to whether they had labor or not after induction, pregnant women were divided into the success group (pregnant women who had labor after induction, 72 cases) and the failure group (pregnant women who did not have labor after induction, 30 cases). Logistic regression was used to analyze the related factors of induction failure in twin pregnant women. Results: The parity and cervical Bishop score in the failure group were significantly lower than those in the success group, while the proportion of dichorionic diamniotic twins, assisted reproductive technology pregnancy and cervical Bishop score <6, postpartum hospital stay and total hospital stay in the failure group were significantly higher than those in the success group (all P<0.05). The proportion of induced labor by artificial rupture of membranes ± oxytocin intravenous infusion in the success group was 72.2% (52/72), which was significantly higher than that in the failure group (46.7%, 14/30; P=0.030). There were no significant differences between the two groups in the gestational age at delivery, the incidence of severe postpartum hemorrhage and blood transfusion, the amount of postpartum hemorrhage, the neonatal weight of two fetuses, the incidence of neonatal asphyxia, and the proportion of neonates admitted to the neonatal intensive care unit (all P>0.05). There were no severe perineal laceration and hysterectomy in all pregnant women. Multivariate logistic regression analysis showed that primipara (OR=3.064, 95%CI: 1.112-8.443; P=0.030) and cervical Bishop score <6 (OR=5.208, 95%CI: 2.008-13.508; P=0.001) were the independent risk factors for induction failure in twin pregnancy. Conclusions: Elective induction of labor in twin pregnancy is safe and feasible. It is helpful to improve the success rate of induction of labor by strictly grasping the timing and indications of termination of pregnancy, choosing the appropriate method of induction according to the condition of the cervix, and actively promoting cervical ripening .


Infant, Newborn , Pregnancy , Female , Humans , Pregnancy Trimester, Third , Pregnancy, Twin , Postpartum Hemorrhage/etiology , Retrospective Studies , Labor, Induced/methods , Cervical Ripening
18.
Basic Res Cardiol ; 119(1): 169-192, 2024 Feb.
Article En | MEDLINE | ID: mdl-38147128

Adult mammalian cardiomyocytes have minimal cell cycle capacity, which leads to poor regeneration after cardiac injury such as myocardial infarction. Many positive regulators of cardiomyocyte cell cycle and cardioprotective signals have been identified, but extracellular signals that suppress cardiomyocyte proliferation are poorly understood. We profiled receptors enriched in postnatal cardiomyocytes, and found that very-low-density-lipoprotein receptor (Vldlr) inhibits neonatal cardiomyocyte cell cycle. Paradoxically, Reelin, the well-known Vldlr ligand, expressed in cardiac Schwann cells and lymphatic endothelial cells, promotes neonatal cardiomyocyte proliferation. Thrombospondin1 (TSP-1), another ligand of Vldlr highly expressed in adult heart, was then found to inhibit cardiomyocyte proliferation through Vldlr, and may contribute to Vldlr's overall repression on proliferation. Mechanistically, Rac1 and subsequent Yap phosphorylation and nucleus translocation mediate the regulation of the cardiomyocyte cell cycle by TSP-1/Reelin-Vldlr signaling. Importantly, Reln mutant neonatal mice displayed impaired cardiomyocyte proliferation and cardiac regeneration after apical resection, while cardiac-specific Thbs1 deletion and cardiomyocyte-specific Vldlr deletion promote cardiomyocyte proliferation and are cardioprotective after myocardial infarction. Our results identified a novel role of Vldlr in consolidating extracellular signals to regulate cardiomyocyte cell cycle activity and survival, and the overall suppressive TSP-1-Vldlr signal may contribute to the poor cardiac repair capacity of adult mammals.


Myocardial Infarction , Thrombospondin 1 , Animals , Mice , Cell Proliferation , Endothelial Cells/metabolism , Ligands , Mammals , Mice, Knockout , Myocardial Infarction/metabolism , Myocytes, Cardiac/metabolism , Regeneration , Thrombospondin 1/metabolism
19.
Exp Biol Med (Maywood) ; 248(23): 2393-2407, 2023 Dec.
Article En | MEDLINE | ID: mdl-38159074

Palmitoylation, which is mediated by protein acyltransferase (PAT) and performs important biological functions, is the only reversible lipid modification in organism. To study the effect of protein palmitoylation on hypopharyngeal squamous cell carcinoma (HPSCC), the expression levels of 23 PATs in tumor tissues of 8 HPSCC patients were determined, and high mRNA and protein levels of DHHC9 and DHHC15 were found. Subsequently, we investigated the effect of 2-bromopalmitate (2BP), a small-molecular inhibitor of protein palmitoylation, on the behavior of Fadu cells in vitro (50 µM) and in nude mouse xenograft models (50 µmol/kg), and found that 2BP suppressed the proliferation, invasion, and migration of Fadu cells without increasing cell apoptosis. Mechanistically, the effect of 2BP on the transduction of BMP, Wnt, Shh, and FGF signaling pathways was tested with qRT-PCR, and its drug target was explored with western blotting and acyl-biotinyl exchange assay. Our results showed that 2BP inhibited the transduction of the FGF/ERK signaling pathway. The palmitoylation level of Ras protein decreased after 2BP treatment, and its distribution in the cell membrane structure was reduced significantly. The findings of this work reveal that protein palmitoylation mediated by DHHC9 and DHHC15 may play important roles in the occurrence and development of HPSCC. 2BP is able to inhibit the malignant biological behaviors of HPSCC cells, possibly via hindering the palmitoylation and membrane location of Ras protein, which might, in turn, offer a low-toxicity anti-cancer drug for targeting the treatment of HPSCC.


Head and Neck Neoplasms , ras Proteins , Mice , Animals , Humans , Squamous Cell Carcinoma of Head and Neck , Palmitates/pharmacology
20.
Exp Appl Acarol ; 91(4): 509-539, 2023 Dec.
Article En | MEDLINE | ID: mdl-37995026

The prevalence of house dust mite (HDM) allergy, especially in Asian countries with rapid urbanization, has been increasing. House dust mites thrive in places with relatively high humidity. With the combination of climate change, naturally high humidity, and urbanization, tropical countries like Malaysia are becoming a hotspot for HDM allergy fast. With a previously reported sensitization rate of between 60 and 80%, it is a worrying trend for Malaysia. However, due to incomplete and out-of-date data, as seen by the limited study coverage in the past, these numbers do not paint a complete picture of the true HDM allergy scene in Malaysia. This review briefly discusses the HDM fauna, the HDM sensitization rate, the common diagnosis and therapeutic tools for HDM allergy in Malaysia, and makes suggestions for possible improvements in the future. This review also highlights the need of more comprehensive population-based prevalence studies to be done in Malaysia, encompassing the three main HDMs-Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Blomia tropicalis-as the lack of up-to-date studies failed to give a clearer picture on the current scenario of HDM allergy in Malaysia. Future studies will be beneficial to the nation in preparing a better blueprint for the management and treatment of HDM allergy.


Dust Mite Allergy , Animals , Malaysia/epidemiology , Evidence Gaps , Pyroglyphidae , Allergens , Dust/analysis , Antigens, Dermatophagoides
...