Improving product quality and productivity of an antibody-based biotherapeutic using inverted frustoconical shaking bioreactors.

The Chinese hamster ovarian (CHO) cells serve as a common choice in biopharmaceutical production, traditionally cultivated in stirred tank bioreactors (STRs). Nevertheless, the pursuit of improved protein quality and production output for commercial purposes demand exploration into new bioreactor types. In this context, inverted frustoconical shaking bioreactors (IFSB) present unique physical properties distinct from STRs. This study aims to compare the production processes of an antibody-based biotherapeutic in both bioreactor types, to enhance production flexibility. The findings indicate that, when compared to STRs, IFSB demonstrates the capability to produce an antibody-based biotherapeutic with either comparable or enhanced bioprocess performance and product quality. IFSB reduces shear damage to cells, enhances viable cell density (VCD), and improves cell state at a 5-L scale. Consequently, this leads to increased protein expression (3.70 g/L vs 2.56 g/L) and improved protein quality, as evidenced by a reduction in acidic variants from 27.0% to 21.5%. Scaling up the culture utilizing the Froude constant and superficial gas velocity ensures stable operation, effective mixing, and gas transfer. The IFSB maintains a high VCD and cell viability at both 50-L and 500-L scales. Product expression levels range from 3.0 to 3.6 g/L, accompanied by an improved acidic variants attribute of 20.6%-22.7%. The IFSB exhibits superior productivity and product quality, underscoring its potential for incorporation into the manufacturing process for antibody-based biotherapeutics. These results establish the foundation for IFSB to become a viable option in producing antibody-based biotherapeutics for clinical and manufacturing applications.

Prediction model of measurement errors in current transformers based on deep learning.

The long-term monitoring stability of electronic current transformers is crucial for accurately obtaining the current signal of the power grid. However, it is difficult to accurately distinguish between the fluctuation of non-stationary random signals on the primary side of the power grid and the gradual error of the transformers themselves. A current transformer error prediction model, CNN-MHA-BiLSTM, based on the golden jackal optimization (GJO) algorithm, which is used to obtain the optimal parameter values, bidirectional long short-term memory (BiLSTM) network, convolutional neural networks (CNNs), and multi-head attention (MHA), is proposed to address the difficulty of measuring error evaluation. This model can be used to determine the operation of transformers and can be widely applied to assist in determining the stability of transformer operation and early faults. First, CNN is used to mine the vertical detail features of error data at a certain moment, improving the speed of error prediction. Furthermore, a cascaded network with BiLSTM as the core is constructed to extract the horizontal historical features of the error data. The GJO algorithm is used to adjust the parameters of the BiLSTM model; optimize the hidden layer nodes, training frequency, and learning rate; and integrate MHA mechanism to promote the model to pay attention to the characteristic changes of the data in order to improve the accuracy of error prediction. Finally, this method is applied to the operation data of transformer in substations, and four time periods of data are selected to verify the model effectiveness of the current transformer dataset. The analysis results of single step and multi-step examples indicate that the proposed model has significant advantages in terms of accuracy and stability in error prediction.

Associations of per- and polyfluoroalkyl substances (PFAS) and their mixture with risk of rheumatoid arthritis in the U.S. adult population.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are known environmental contaminants with immunosuppressive properties. Their connection to rheumatoid arthritis (RA), a condition influenced by the immune system, is not well studied. This research explores the association between PFAS exposure and RA prevalence. METHODS: This research utilized data from the NHANES, encompassing a sample of 10,496 adults from the 2003-2018 cycles, focusing on serum levels of several PFAS. The presence of RA was determined based on self-reports. This study used multivariable logistic regression to assess the relationship between individual PFAS and RA risk, adjusting for covariates to calculate odds ratios (ORs). The combined effects of PFAS mixtures were evaluated using BKMR, WQS regression, and quantile g-computation. Additionally, sex-specific associations were explored through stratified analysis. RESULTS: Higher serum PFOA (OR = 0.88, 95% CI: 0.79, 0.98), PFHxS (OR = 0.91, 95% CI: 0.83, 1.00), PFNA (OR = 0.87, 95% CI: 0.77, 0.98), and PFDA (OR = 0.89, 95% CI: 0.81, 0.99) concentration was related to lower odds of RA. Sex-specific analysis in single chemical models indicated the significant inverse associations were only evident in females. BKMR did not show an obvious pattern of RA estimates across PFAS mixture. The outcomes of sex-stratified quantile g-computation demonstrated that an increase in PFAS mixture was associated with a decreased odds of RA in females (OR: 0.76, 95% CI: 0.62, 0.92). We identified a significant interaction term of the WQS*sex in the 100 repeated hold out WQS analysis. Notably, a higher concentration of the PFAS mixture was significantly associated with reduced odds of RA in females (mean OR = 0.93, 95% CI: 0.88, 0.98). CONCLUSIONS: This study indicates potential sex-specific associations of exposure to various individual PFAS and their mixtures with RA. Notably, the observed inverse relationships were statistically significant in females but not in males. These findings contribute to the growing body of evidence indicating that PFAS may have immunosuppressive effects.

Aminoazanium of A-site Cations in Metal-Free Halide Perovskite Single Crystals to Reduce Thermal Expansion for Efficient X-ray Detection.

Metal-free perovskites (MFPs) have recently become a newcomer in X-ray detection due to their flexibility and low toxicity characteristics. However, their photoelectronic properties and stability should be further improved mainly through materials design. Here, the aminoazanium of DABCO2+ was developed for the preparation of NDABCO-NH4Br3 (NDABCO = N-amino-N'-diazabicyclo[2.2.2]octonium) single crystals (SCs), and its physical properties, intermolecular interactions, and device performance were systematically explored. Notably, NDABCO-NH4Br3 can achieve improved stability by enlarging defect formation energy and inducing abundant intermolecular forces. Moreover, the slight lattice distortion could ensure the weakening electron-phonon coupling for improving carrier transport. In particular, the slight lattice distortion after the long-chain NDABCO2+ introduction could retard thermal expansion for the preparation of high-quality crystals. Finally, the corresponding X-ray detector delivered a moderate sensitivity of 623.3 µC Gyair-1 cm-2. This work provides a novel strategy through rationally designed organic cations to balance the material stability and device performance.

Oblique conformal anastomosis decreased the risks of cervical anastomotic leakage after totally minimally invasive esophagectomy.

OBJECTIVE: To investigate the effectiveness of the original oblique conformal anastomosis presented in this research in reducing the incidence of cervical anastomotic leak after performing totally minimally invasive esophagectomy (TMIE). METHODS: The esophagus and stomach of 27 fresh pigs, termed the esophagogastric model, were used to simulate human esophagogastric organs for this study's in vitro experimental objectives. Nine esophagogastric models of similar weight were divided into three groups. Esophagogastrostomy with circular-stapled end-to-side anastomosis was performed. A tension gauge was used to pull the anastomosis, and the tension at which anastomotic leakage occurred was recorded. Furthermore, a retrospective assessment of 539 patients who underwent TMIE was conducted to analyze the influencing factors of cervical anastomotic leakage. RESULTS: Experiments on the esophagogastric models showed a higher fracture strength of oblique conformal anastomosis than that of conventional anastomosis (F2,18 = 40.86, P < 0.05), which was associated with a lower incidence of cervical anastomotic leakage (X2 = 9.0260, P = 0.0027). Retrospective analysis of 539 esophageal cancer patients who underwent TMIE showed that in contrast to conventional anastomosis, oblique conformal anastomosis was an independent protective factor against cervical anastomotic leakage (P = 0.0462, OR = 0.5872, 95% CI = 0.3497-0.9993). CONCLUSION: Oblique conformation anastomosis was stronger and involved a more prominent reduced risk of cervical anastomotic leakage than conventional anastomosis after TMIE.

In Vivo Toxicology of Metabolizable Atomically Precise Au25 Clusters at Ultrahigh Doses.

Ultrasmall Au25(MPA)18 clusters show great potential in biocatalysts and bioimaging due to their well-defined, tunable structure and properties. Hence, in vivo pharmacokinetics and toxicity of Au nanoclusters (Au NCs) are very important for clinical translation, especially at high dosages. Herein, the in vivo hematological, tissue, and neurological effects following exposure to Au NCs (300 and 500 mg kg-1) were investigated, in which the concentration is 10 times higher than in therapeutic use. The biochemical and hematological parameters of the injected Au NCs were within normal limits, even at the ultrahigh level of 500 mg kg-1. Meanwhile, no histopathological changes were observed in the Au NC group, and immunofluorescence staining showed no obvious lesions in the major organs. Furthermore, real-time near-infrared-II (NIR-II) imaging showed that most of the Au25(MPA)18 and Au24Zn1(MPA)18 can be metabolized via the kidney. The results demonstrated that Au NCs exhibit good biosafety by evaluating the manifestation of toxic effects on major organs at ultrahigh doses, providing reliable data for their application in biomedicine.

Surface functionalized titanium nitride electrode for CMOS compatible bioelectronic devices.

In this study, a surface functionalization approach by covalent grafting of an organic thin film containing hydroxyl groups on TiN surface via electroreduction of diazonium salts "4-(2-hydroxyethyl)benzenediazonium salt" is presented. Cyclic voltammetry procedures were carried out at the potential ranges of -0.8 V~0.5 V (vs Ag/AgCl) with varying numbers of potential cycles (i.e., 5, 25, and 50 cycles) in order to study the thickness of modification layer. Then, the electrochemical properties, surface morphology, and chemical structures of the sample before and after modifications were investigated via multiple characterization techniques, such as cyclic voltammetry (CV), atomic force microscopy (AFM), scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS), etc., thereby confirming the successful grafting of hydroxyl groups onto the TiN surface. The experiments on DNA synthesis aimed to explore the potential of modified TiN electrode as a novel platform for DNA data storage applications and the corresponding proof-of-principle was accomplished by the process of coupling Cy3-phosphoramidite. Finally, the experiments were successfully reproduced on the randomly selected sites of the modified TiN microarray chips demonstrating the potential of technical protocol to extend applications in future bioelectronic devices, such as bio-sensing, high-throughput DNA synthesis, and molecular manipulation.

Ultrahigh-Performance Fiber-Supported Iron-Based Ionic Liquid for Synthesizing 3,4-Dihydropyrimidin-2-(1H)-ones in a Cleaner Manner.

Herein, a fiber-supported iron-based ionic liquid as a type of fibrous catalyst has been developed for the synthesis of bioactive 3,4-dihydropyrimidin-2-(1H)-ones (DHPMs) via three-component Biginelli reactions in a cleaner manner. The described fibrous catalyst was obtained from the commercially available polyetheretherketone (PEEK) fiber by postfunctionalization processes and was characterized and analyzed in detail by means of diversified technologies. Furthermore, the fiber-supported iron-based ionic liquids could mediate the classical three-component Biginelli reactions to proceed smoothly to gain a variety of substituted DHPMs with yields of up to 99%. The superior catalytic activities of the fibrous catalyst were ascribed to the quasi-homogeneous medium by ionic liquids generated in the surface layer of the PEEK fiber, which could afford an appropriate reaction zone and could further be available for the aggregation of substrates to facilitate the three-component reaction. Notably, the fibrous catalyst is available for recycling over 10 runs just by a pair of tweezers, and the operational procedure was capable of enlarging the catalytic system to the gram-scale without any performance degradation, which provided a cleaner manner to take advantage of the iron-based catalyst in organic synthesis with potential industrialization prospects.

[Efficacy and Safety of Medical Thoracoscopic Bulla Volume Reduction in the Treatment of Chronic Obstructive Pulmonary Disease Combined With Giant Emphysematous Bullae]. / ç»å† ç§‘èƒ¸è ”é•œè‚ºå¤§ç–±å‡å®¹æœ¯æ²»ç–—æ ¢æ€§é˜»å¡žæ€§è‚ºç–¾ç— åˆå¹¶å·¨åž‹è‚ºå¤§ç–±çš„ç–—æ•ˆå’Œå®‰å ¨æ€§ç ”ç©¶.

Objective: To explore the efficacy and safety of medical thoracoscopic bulla volume reduction for the treatment of chronic obstructive pulmonary disease (COPD) combined with giant emphysematous bullae (GEB). Methods: A total of 66 patients with COPD combined with GEB were enrolled in the study. All the subjects received treatment at Zhengzhou Central Hospital affiliated with Zhengzhou University between March 2021 and December 2022. The subjects were divided into two groups, a medical thoracoscope group consisting of 30 cases treated with medical thoracoscopic bulla volume reduction and a surgical thoracoscope group consisting of 36 cases treated by video-assisted thoracoscopic surgery. All patients were followed up before discharge and 3 months and 6 months after discharge. The preoperative and postoperative levels of the pulmonary function, 6-minute walk distance (6MWD), and St. George's Respiratory Questionnaire (SGRQ) scores and differences in postoperative complications were compared between the two groups. The operative duration, postoperative length-of-stay, and surgical costs and hospitalization bills, and the maximum visual analog scale (VAS) pain scores at 24 h after the procedure were assessed. Results: The baseline data of the two groups were comparable, showing no statistically significant difference. The forced expiratory volume in 1 second (FEV1) 6 months after the procedures improved in both the medical thoracoscopy group ([0.78±0.29] L vs. [1.02±0.31] L, P<0.001) and the surgical thoracoscopy group ([0.80±0.21] L vs. [1.03±0.23] L, P<0.001) compared to that before the procedures. Improvements to a certain degree in 6MWT and SGRQ scores were also observed in the two groups at 3 months and 6 months after the procedures (P<0.05). In addition, no statistically significant difference in these indexes was observed during the follow-up period of the patients in the two groups. There was no significant difference in operating time between the two groups. The medical thoracoscopy group had shorter postoperative length-of-stay ([7.3±2.6] d) and 24-hour postoperative VAS pain scores (3.0 [2.0, 3.3]) than the surgical thoracoscopic group did ([10.4±4.3] d and 4.5 [3.0, 5.0], respectively), with the differences being statistically significant (P<0.05). Surgical cost and total hospitalization bills were lower in the medical thoracoscopy group than those in the surgical thoracoscopy group (P<0.05). The complication rate in the medical thoracoscopy group was lower than that in the surgical thoracoscopy group (46.7% vs. 52.8%), but the difference was not statistically significant. Conclusion: Medical thoracoscopic reduction of bulla volume can significantly improve the pulmonary function, quality of life, and exercise tolerance of patients with COPD combined with GEB, and it can reduce postoperative short-term pain and shorten postoperative length-of-stay. The procedure has the advantages of minimal invasiveness, quick recovery, and low costs. Hence extensive clinical application is warranted.

High-throughput DNA synthesis for data storage.

With the explosion of digital world, the dramatically increasing data volume is expected to reach 175 ZB (1 ZB = 1012 GB) in 2025. Storing such huge global data would consume tons of resources. Fortunately, it has been found that the deoxyribonucleic acid (DNA) molecule is the most compact and durable information storage medium in the world so far. Its high coding density and long-term preservation properties make itself one of the best data storage carriers for the future. High-throughput DNA synthesis is a key technology for "DNA data storage", which encodes binary data stream (0/1) into quaternary long DNA sequences consisting of four bases (A/G/C/T). In this review, the workflow of DNA data storage and the basic methods of artificial DNA synthesis technology are outlined first. Then, the technical characteristics of different synthesis methods and the state-of-the-art of representative commercial companies, with a primary focus on silicon chip microarray-based synthesis and novel enzymatic DNA synthesis are presented. Finally, the recent status of DNA storage and new opportunities for future development in the field of high-throughput, large-scale DNA synthesis technology are summarized.

Construction of active-inert core-shell structured nanocrystals for broad range multicolor upconversion luminescence.

Rare earth doped up-conversion luminescent nano-materials exhibit abundant emission colors under suitable excitation condition. In this work, NaYF4:Er/Ho@NaYF4 and NaYbF4:Tm@NaYF4 nanoparticles were synthesized by co-precipitation method. The pure red emission can be realized by the designed NaYF4:Er/Ho@NaYF4 nanocrystals and the R/Gs reach 23.3 and 25 under excitations of 980 and 1550 nm lasers, respectively. The R/G declines as the power increasing with the emission color changing from red to yellow, which is due to the quick saturation of the energy levels, radiating red emissions. Meanwhile, the emission intensity of NaYbF4:Tm@NaYF4 nanocrystals increases by 58.3 folds after encasing the inert shell NaYF4 and the CIE color coordinate reaches (0.1646, 0.0602) under 980 nm laser excitation. Furthermore, broad range multicolor from blue to red and yellow up-conversion emissions is achieved by mixing NaYF4:Er/Ho@NaYF4 and NaYbF4:Tm@NaYF4 nanocrystals, which could be applied to colorful displaying, security anti-counterfeiting and information coding.

Germline Genetic NBN Variation and Predisposition to B-cell Acute Lymphoblastic Leukemia in Children.

Biallelic mutation in the DNA-damage repair gene NBN is the genetic cause of Nijmegen Breakage Syndrome, which is associated with predisposition to lymphoid malignancies. Heterozygous carriers of germline NBN variants may also be at risk for leukemia development, although this is much less characterized. Sequencing 4,325 pediatric B-ALL patients, we systematically examined the frequency of germline NBN variants and identified 25 unique, putatively damaging NBN coding variants in 50 patients. Compared with the frequency of NBN variants in gnomAD non-cancer controls (189 unique, putatively damaging NBN coding variants in 472 of 118,479 individuals) we found significant overrepresentation in pediatric B-ALL (p=0.004, OR=1.8). Most B-ALL-risk variants were missense and cluster within the NBN N-terminal domains. Using two functional assays, we verified 14 of 25 variants with severe loss-of-function phenotypes and thus classified these as non-functional or partially functional. Finally, we found that germline NBN variant carriers, all of which were identified as heterozygous genotypes, showed similar survival outcomes relative to those with WT status. Taken together, our findings provide novel insights into the genetic predisposition to B-ALL, and the impact of NBN variants on protein function and suggest that heterozygous NBN variant carriers may safely receive B-ALL therapy.

Particulate matter emissions from light-duty gasoline vehicles under different ambient temperatures: Physical properties and chemical compositions.

Fine particulate matter (PM2.5) from vehicle exhaust is typically emitted at breathing height and thus imposes severe adverse effects on human health and air quality. However, there is currently limited knowledge on the characteristics of PM2.5 in exhaust, specifically its chemical components, at different ambient temperatures. Particulate emissions from typical light-duty gasoline vehicles (LDGVs) were investigated on a chassis dynamometer according to the Worldwide Harmonized Light-Duty Test Cycle at ambient temperatures of 38 °C, 28 °C, 15 °C, 5 °C and - 7 °C. The results showed a significant increase in particulate mass (PM) and particle number (PN) emissions with decreasing ambient temperature, particularly during cold starts below 5 °C. The particle size distributions exhibited distinct bimodal patterns, with accumulation-mode (AM) particles (60-125 nm) dominating the gasoline direct injection (GDI) distribution and nucleation-mode (NM) particles (8-12 nm) dominating the port fuel injection (PFI) distribution. AM particles were more temperature-sensitive than NM particles. Lower temperatures produced higher emissions of elements, carbonaceous components, and large-ring polycyclic aromatic hydrocarbons, while water-soluble ions showed an opposite trend. The total toxic equivalent, primarily influenced by benzo[a]pyrene, was significantly higher at -7 °C. The penalty distribution of LDGV PM and PN, defined by comparing the emissions at the various temperatures to those at regulated temperatures (23-30 °C), exhibited notable temporal heterogeneity (winter > autumn > spring > summer) and spatial heterogeneity (northern China > southern China). These findings are essential for establishing more stringent vehicle emission standards and improving emission models in cold environments.

Photothermal Mineralization of Polyolefin Microplastics via TiO2 Hierarchical Porous Layer-Based Semiwetting Air-Plastic-Solid Interfaces.

Photo-mineralization of microplastics under mild conditions has emerged as a promising solution to plastic waste disposal. However, the inadequate contact between oxygen, water-insoluble polyolefin microplastics, and photocatalysts remains a critical issue. In this study, a TiO2 hierarchical porous layer (TiO2-HPL) photocatalyst is presented to establish air-plastic-solid triphase interfaces for the photothermal mineralization of polyolefins. The wettability of the TiO2-HPL-based triphase interface is finely controlled from plastophobic to plastophilic. High-resolution imaging and finite element simulation demonstrate the significance of a semiwetting state in achieving multidirectional oxygen diffusion through the hierarchical pore structure while maintaining sufficient contact between the plastic phase and photocatalysts. For low-density polyethylene, the TiO2-HPL achieves a photothermal mineralization rate of 5.63 mmol g-1 h-1 and a conversion of 26.3% after 20 h of continuous irradiation. Additionally, the triphase photocatalytic system with semiwetting gas-plastic-solid interfaces shows good universality for various polyolefin reagents and products, illustrating its potential in achieving efficient photothermal mineralization of non-degradable microplastics.

An evidence-based guideline on treating lumbar disc herniation with traditional Chinese medicine.

BACKGROUND: Lumbar disc herniation (LDH), as one of the most common causes of lower back pain, imposes a heavy economic burden on patients and society. Conservative management is the first-line choice for the majority of LDH patients. Traditional Chinese medicine (TCM) is an important part of conservative treatment and has attracted more and more international attention. STUDY DESIGN: Evidence-based guideline. METHODS: We formed a guideline panel of multidisciplinary experts. The clinical questions were identified on the basis of a systematic literature search and a consensus meeting. We searched the literature for direct evidence on the management of LDH and assessed its certainty-generated recommendations using the grading of recommendations, assessment, development, and evaluation (GRADE) approach. RESULTS: The guideline panel made 20 recommendations, which covered the use of Shentong Zhuyu decoction, Shenzhuo decoction, Simiao San decoction, Duhuo Jisheng decoction, Yaobitong capsule, Yaotongning capsule, Osteoking, manual therapy, needle knife, manual acupuncture, electroacupuncture, Chinese exercise techniques (Tai Chi, Baduanjin, or Yijinjing), and integrative medicine, such as combined non-steroidal anti-inflammatory drugs, neural nutrition, and traction. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. CONCLUSION: This is the first LDH treatment guideline for TCM and integrative medicine with a systematic search, synthesis of evidence, and using the GRADE method to rate the quality of evidence. We hope these recommendations can help support healthcare workers caring for LDH patients.

Tailoring therapeutics via a systematic beneficial elements comparison between photosynthetic bacteria-derived OMVs and extruded nanovesicles.

Photosynthetic bacteria (PSB) has shown significant potential as a drug or drug delivery system owing to their photothermal capabilities and antioxidant properties. Nevertheless, the actualization of their potential is impeded by inherent constraints, including their considerable size, heightened immunogenicity and compromised biosafety. Conquering these obstacles and pursuing more effective solutions remains a top priority. Similar to extracellular vesicles, bacterial outer membrane vesicles (OMVs) have demonstrated a great potential in biomedical applications. OMVs from PSB encapsulate a rich array of bioactive constituents, including proteins, nucleic acids, and lipids inherited from their parent cells. Consequently, they emerge as a promising and practical alternative. Unfortunately, OMVs have suffered from low yield and inconsistent particle sizes. In response, bacteria-derived nanovesicles (BNVs), created through controlled extrusion, adeptly overcome the challenges associated with OMVs. However, the differences, both in composition and subsequent biological effects, between OMVs and BNVs remain enigmatic. In a groundbreaking endeavor, our study meticulously cultivates PSB-derived OMVs and BNVs, dissecting their nuances. Despite minimal differences in morphology and size between PSB-derived OMVs and BNVs, the latter contains a higher concentration of active ingredients and metabolites. Particularly noteworthy is the elevated levels of lysophosphatidylcholine (LPC) found in BNVs, known for its ability to enhance cell proliferation and initiate downstream signaling pathways that promote angiogenesis and epithelialization. Importantly, our results indicate that BNVs can accelerate wound closure more effectively by orchestrating a harmonious balance of cell proliferation and migration within NIH-3T3 cells, while also activating the EGFR/AKT/PI3K pathway. In contrast, OMVs have a pronounced aptitude in anti-cancer efforts, driving macrophages toward the M1 phenotype and promoting the release of inflammatory cytokines. Thus, our findings not only provide a promising methodological framework but also establish a definitive criterion for discerning the optimal application of OMVs and BNVs in addressing a wide range of medical conditions.

Analysis of Genetic Diversity and Structure of Eight Populations of Nerita yoldii along the Coast of China Based on Mitochondrial COI Gene.

Nerita yoldii is a euryhaline species commonly found in the intertidal zone. To investigate the genetic diversity of 233 N. yoldii individuals from eight locations along the coast of China, we utilized the mitochondrial COI gene as a molecular marker. A total of 34 haplotypes were detected, exhibiting a mean haplotype diversity (Hd) of 0.5915 and a mean nucleotide diversity (Pi) of 0.0025, indicating high levels of genetic diversity among all populations. An analysis of molecular variance (AMOVA) indicated that the primary source of genetic variation occurs within populations. In addition, neutral tests and mismatch analyses suggested that N. yoldii populations may have experienced bottleneck events. Moderate genetic differentiation was observed between Xiapu and other populations, excluding the Taizhou population, and may be attributed to the ocean currents. Intensively studying the genetic variation and population structure of N. yoldii populations contributes to understanding the current population genetics of N. yoldii in the coastal regions of China. This not only provides a reference for the study of other organisms in the same region but also lays the foundation for the systematic evolution of the Neritidae family.

Signal Transducer and Activator of Transcription 4-Induced Up-Regulated LINC01278 Enhances Proliferation and Invasion of Non-Small Cell Lung Cancer Cells via the MicroRNA-877-5p/Activating Transcription Factor 4 Axis.

BACKGROUND: The purpose of this study was to investigate the specific effects of signal transducer and activator of transcription 4 (STAT4)-induced long intergenic nonprotein coding RNA 1278 (LINC01278) on the growth of non-small cell lung cancer (NSCLC) cells involved in the microRNA (miR)-877-5p/activated transcription factor 4 (ATF4) axis. METHODS: NSCLC tumor tissue and adjacent normal tissue were collected. Human normal lung epithelial cell BEAS-2B and human NSCLC cell lines (H1299, H1975, A549, H2228) were collected. The expression levels of STAT4, LINC01278, miR-877-5p, and ATF4 were detected. A549 cells were screened for subsequent experiments. The proliferation ability of cells was detected by colony formation experiment. Cell apoptosis was tested by flow cytometry. Scratch test and transwell assay were used to detect the migration and invasion ability of cells. Biological function of LINC01278 in NSCLC was confirmed by xenograft experiments. RESULTS: Low expression miR-877-5p and high expression of STAT4, LINC01278 and ATF4 were detected in NSCLC. Silenced LINC01278 in A549 cell depressed cell proliferation, migration and invasion, but facilitated cell apoptosis. LINC01278 was positively correlated with STAT4 and could directly bind to miR-877-5p. Upregulating miR-877-5p suppressed NSCLC cell progression, while downregulating miR-877-5p had the opposite effect. Upregulating miR-877-5p abrogated the effects of silenced LINC01278 on NSCLC cell progression. MiR-877-5p targeted ATF4. ATF4 upregulation could partly restore the carcinogenic effect of LINC01278 in vitro and in vivo. CONCLUSION: Our data supports that STAT4-induced upregulation of LINC01278 promotes NSCLC progression by modulating the miR-877-5p/ATF4 axis, suggesting a novel direction for NSCLC treatment.

Neonatal stress disrupts the glymphatic system development and increases the susceptibility to Parkinson's disease in later life.

INTRODUCTION: Neonatal stress disrupts brain development and increases the risk of neurological disorders later in life. However, the impact of neonatal stress on the development of the glymphatic system and susceptibility to Parkinson's disease (PD) remains largely unknown. METHODS: Neonatal maternal deprivation (NMD) was performed on mice for 14 consecutive days to model chronic neonatal stress. Adeno-associated virus expressing A53T-α-synuclein (α-syn) was injected into the substantia nigra to establish PD model mice. Glymphatic activity was determined using in vivo magnetic resonance imaging, ex vivo fluorescence imaging and microplate assay. The transcription and expression of aquaporin-4 (AQP4) and other molecules were evaluated by qPCR, western blotting, and immunofluorescence. Animal's responses to NMD and α-syn overexpression were observed using behavioral tests. RESULTS: Glymphatic activity was impaired in adult NMD mice. AQP4 polarization and platelet-derived growth factor B (PDGF-B) signaling were reduced in the frontal cortex and hippocampus of both young and adult NMD mice. Furthermore, exogenous α-syn accumulation was increased and PD-like symptoms were aggravated in adult NMD mice. CONCLUSION: The results demonstrated that NMD could disrupt the development of the glymphatic system through PDGF-B signaling and increase the risk of PD later in life, indicating that alleviating neonatal stress could be beneficial in protecting the glymphatic system and reducing susceptibility to neurodegeneration.