Modeling assessment of air pollution control measures and COVID-19 pandemic on air quality improvements over Greater Bay Area of China.

A remarkable progress has been made toward the air quality improvements over the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) of China from 2017 to 2020. In this study, for the first time, the emission reductions of regional control measures together with the COVID-19 pandemic were considered simultaneously into the development of the GBA's emission inventories for the years of 2017 and 2020. Based on these collective emission inventories, the impacts of control measures, meteorological variations together with temporary COVID-19 lockdowns on the five major air quality index pollutants (SO2, NO2, PM2.5, PM10, and O3, excluding CO) were evaluated using the WRF-CMAQ and SMAT-CE model attainment assessment tool over the GBA region. Our results revealed that control measures in the Pearl River Delta (PRD) region affected significantly the GBA, resulting in pollutant reductions ranging from 48 % to 64 %. In contrast, control measures in Hong Kong and Macao contributed to pollutant reductions up to 10 %. In PRD emission sectors, stationary combustion, on-road, industrial processes and dust sectors stand out as the primary contributors to overall air quality improvements. Moreover, the COVID-19 pandemic during period I (Jan 23-Feb 23) led to a reduction of NO2 concentration by 7.4 %, resulting in a negative contribution (disbenefit) for O3 with an increase by 2.4 %. Our findings highlight the significance of PRD control measures for the air quality improvements over the GBA, emphasizing the necessity of implementing more refined and feasible manageable joint prevention and control policies.

The ultrasound-based radiomics-clinical machine learning model to predict papillary thyroid microcarcinoma in TI-RADS 3 nodules.

Background: Conventional ultrasound (CUS) technology has proven to be successful in the identification of thyroid nodules. Moreover, the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) was developed for the purpose of evaluating the risk of thyroid nodules based on ultrasound imaging. Nevertheless, identifying papillary thyroid microcarcinoma (PTMC) from TI-RADS 3 nodules using this system can be difficult due to overlapping morphological features. The main objective of this study was to investigate the efficacy of a machine learning model that utilizes ultrasound-based radiomics features and clinical information in accurately predicting the presence of PTMC in TI-RADS 3 nodules. Methods: A total of 221 patients with TI-RADS 3 nodules were included, consisting of 91 cases of PTMC and 130 benign thyroid nodules. They were randomly divided into training and test cohort in an 8:2 ratio. Radiomics features were extracted from CUS images by manually outlining the targets, while clinical parameters were obtained from electronic medical records. The radiomics model, clinical model, and combined model were constructed and validated to distinguish between PTMC and benign thyroid nodules. Radiomics variables were extracted via the Pyradiomics package (V1.3.0). Moreover, least absolute shrinkage and selection operator (LASSO) regression was used for feature selection. Light Gradient Boosting Machine (LightGBM) was employed to build both radiomics and clinical models. Ultimately, a radiomics-clinical model, which fused radiomics features with clinical information, was developed. Results: Among a total of 1,477 radiomics features, fifteen features that were found to be associated with PTMC through univariate analysis and LASSO regression were selected for the development of the radiomics model. The combined "radiomics-clinical" model demonstrated superior diagnostic accuracy compared to the clinical model for distinguishing PTMC in both the training dataset [area under receiver operating curve (AUC): 0.975 vs. 0.845] and the validation dataset (AUC: 0.898 vs. 0.811). We constructed a radiomics-clinical nomogram, and the clinical applicability was confirmed through decision curve analysis. Conclusions: Utilizing an ultrasound-based radiomics approach has proven to be effective in predicting PTMC in patients with TI-RADS 3 nodules.

Selenium-SelK-GPX4 axis protects nucleus pulposus cells against mechanical overloading-induced ferroptosis and attenuates senescence of intervertebral disc.

Intervertebral disc degeneration (IVDD) is one of the most prevalent spinal degenerative disorders and imposes places heavy medical and economic burdens on individuals and society. Mechanical overloading applied to the intervertebral disc (IVD) has been widely recognized as an important cause of IVDD. Mechanical overloading-induced chondrocyte ferroptosis was reported, but the potential association between ferroptosis and mechanical overloading remains to be illustrated in nucleus pulposus (NP) cells. In this study, we discovered that excessive mechanical loading induced ferroptosis and endoplasmic reticulum (ER) stress, which were detected by mitochondria and associated markers, by increasing the intracellular free Ca2+ level through the Piezo1 ion channel localized on the plasma membrane and ER membrane in NP cells. Besides, we proposed that intracellular free Ca2+ level elevation and the activation of ER stress are positive feedback processes that promote each other, consistent with the results that the level of ER stress in coccygeal discs of aged Piezo1-CKO mice were significantly lower than that of aged WT mice. Then, we confirmed that selenium supplementation decreased intracellular free Ca2+ level by mitigating ER stress through upregulating Selenoprotein K (SelK) expression. Besides, ferroptosis caused by the impaired production and function of Glutathione peroxidase 4 (GPX4) due to mechanical overloading-induced calcium overload could be improved by selenium supplementation through Se-GPX4 axis and Se-SelK axis in vivo and in vitro, eventually presenting the stabilization of the extracellular matrix (ECM). Our findings reveal the important role of ferroptosis in mechanical overloading-induced IVDD, and selenium supplementation promotes significance to attenuate ferroptosis and thus alleviates IVDD, which might provide insights into potential therapeutic interventions for IVDD.

Effect of Cobalt and Chromium Content on Microstructure and Properties of WC-Co-Cr Coatings Prepared by High-Velocity Oxy-Fuel Spraying.

To explore the Co/Cr ratio impact on the high-velocity oxygen fuel (HVOF)-sprayed WC-Co-Cr coatings microstructure and performances, three kinds of WC-Co-Cr coatings, namely WC-4Co-10Cr, WC-7Co-7Cr, and WC-10Co-4Cr, were prepared by using a high-velocity oxygen fuel (HVOF) spraying process. The three coatings' phase composition, microstructure, basic mechanical properties, abrasive wear, and corrosion resistance were investigated. The results show that all three WC-Co-Cr coatings comprise the main phase WC, minor W2C, and amorphous W-Co-Cr phase, besides the WC-4Co-10Cr coating containing a small amount of CrxCy phase. In addition, WC-7Co-7Cr coating exhibited the highest hardness and abrasive wear resistance, followed by WC-10Co-4Cr and WC-4Co-10Cr coatings. The corrosion resistance as a hierarchy was found to be WC-10Co-4Cr > WC-7Co-7Cr > WC-4Co-10Cr.

Proteins from Blackberry Seeds: Extraction, Osborne Isolate, Characteristics, Functional Properties, and Bioactivities.

Blackberry fruit contains high levels of nutrients and phenolic compounds. Blackberry pomace accounts for 20~30% of its whole fruit during processing and is generally treated as fertilizer. Blackberry pomace has many seeds that contain carbohydrates, polyphenols, flavonoids, pectin, protein, and other bioactive nutrients. However, its functional properties and seed protein compositions have not been reported. We used a single-factor experiment, response surface, and Osborne isolate method to extract protein isolate, albumin, globulin, glutelin, and prolamin from blackberry seeds for the first time and evaluated their characteristics and functional properties. Glutelin and protein isolate showed good water-holding capacity, emulsification, and foaming capacity, while albumin and globulin showed good oil-holding capacity and thermal stability. They were found to have good antioxidant activities that might be good DPPH free radical scavengers, especially prolamin, which has the lowest IC50 value (15.76 µg/mL). Moreover, globulin had the lowest IC50 value of 5.03 µg/mL against Hela cells, 31.82 µg/mL against HepG2 cells, and 77.81 µg/mL against MCF-7 cells and a high selectivity index (SI), which suggested globulin had better anti-cervical, antihepatoma, and anti-breast activity but relatively low cytotoxicity. These seed proteins may have great prospects for the development and application of food and drugs in the future.

X-ray Detectors Based on Ga2O3 Microwires.

X-ray detectors have numerous applications in medical imaging, industrial inspection, and crystal structure analysis. Gallium oxide (Ga2O3) shows potential as a material for high-performance X-ray detectors due to its wide bandgap, relatively high mass attenuation coefficient, and resistance to radiation damage. In this study, we present Sn-doped Ga2O3 microwire detectors for solar-blind and X-ray detection. The developed detectors exhibit a switching ratio of 1.66 × 102 under X-ray irradiation and can operate stably from room temperature to 623 K, which is one of the highest reported operating temperatures for Ga2O3 X-ray detectors to date. These findings offer a promising new direction for the design of Ga2O3-based X-ray detectors.

Design of an off-axis axiparabola with inclined wavefront correction to obtain a straight focal line.

The axiparabola is a novel reflective element proposed in recent years, which can generate a long focal line with high peak intensity, and has important applications in laser plasma accelerators. The off-axis design of an axiparabola has the advantage of separating the focus from incident rays. However, an off-axis axiparabola designed by the current method always produces a curved focal line. In this paper, we propose a new method to design its surface by combining geometric optics design and diffraction optics correction, which can effectively convert a curved focal line into a straight foal line. We reveal that the geometric optics design inevitably introduces an inclined wavefront, which leads to the bending of the focal line. To compensate for the tilt wavefront, we use an annealing algorithm to further correct the surface through diffraction integral operation. We also carry out numerical simulation verification based on scalar diffraction theory, which proves that the surface of this off-axis mirror designed by this method can always obtain a straight focal line. This new method has wide applicability in an axiparabola with any off-axis angle.

Stabilization of Bio-Oss® particulates using photocurable hydrogel to enhance bone regeneration by regulating macrophage polarization.

Bone substitutes are widely used in maxillofacial and oral surgeries. However, in clinical practice, bone substitutes with various forms, including separated particulates, powders, and blocks, have exhibited poor handling properties and space maintenance characteristics, resulting in long surgery procedures and unstable volume of the newly formed bone. Movable separated particulates with high stiffness have induced local inflammatory responses that hinder bone regeneration. The present study aimed to develop a new method to enhance the stability and operability of bone substitutes commonly used in dentistry by premixing with photocurable hydrogel GelMA. The GelMA-encapsulated particulate had a strong capacity to aggregate separated particulates and firmly attach to the host bone defect after photocuring compared to particulates alone. Additionally, macrophages at the surface of the GelMA-stabilized particulates tended to present a more M2-like phenotype than those at the surface of Bio-Oss®, leading to more MMR+ multinucleated giant cell formation and the induction of blood vessel invasion and new bone formation. In conclusion, this hydrogel-coated bone substitute strategy facilitates bone regeneration with increased operability, a stable volume of osteogenic space, and a favorable osteogenic microenvironment, indicating its potential value in the field of maxillofacial and oral surgeries when bone substitutes are needed.

Analysis of risk factors for duodenal leak after repair of a duodenal perforation.

BACKGROUND: Repairing of a duodenal perforation is a well accepted procedure, but clinically, approximately 4% of patients develop duodenal leaks after perforation repair, increasing the risk of death. We retrospectively analyzed clinical data from 168 patients at our hospital to explore risk factors for duodenal leak after perforation repair and developed a nomogram for predicting postoperative duodenal leak. METHODS: This retrospective case-control study totalled 168 patients undergoing repair of a duodenal perforation with omentopexy at the General Surgery Department, Dongnan Hospital of Xiamen University, from January 2012 to January 2022. The patients were divided into the non-leak group and the leak group. Risk factors were evaluated by analyzing the patient's sex, shock, diameter and anatomic position of the ulcer, use of NSAIDS and Glucocorticoid, history of drinking, diabetes, chronic diseases, age, time of onset of symptoms and lab tests. RESULT: One hundred fifty-six patients (92.9%) who did not develop leaks after repair of a duodenal perforation were included in the non-leak group, and 12 (7.1%) developed leaks were included in the leak group. In univariate analysis, there were significant differences between the two groups referring to age, shock, NSAIDs, albumin, and perforation size (P < 0.05). The area under the ROC curve for perforation diameter was 0.737, the p-value was 0.006, the optimal cutoff point was 11.5, sensitivity was 58.3%, and specificity was 93.6%, the positive predictive value is 41.1%, and the negative predictive value is 98.0%. In the internal validation of the performance of the nomogram, the C-index and AUC of the model were 0.896(95%CI 0.81-0.98), demonstrating that the nomogram model was well calibrated. CONCLUSION: The study discussed the risk factors for postoperative duodenal leak in patients undergoing repair of a duodenal perforation, and a nomogram was constructed to predict the leak. Future prospective studies with large sample sizes and multiple centres are needed to further elucidate the risk of duodenal leak after repair of a duodenal perforation.

Root Niches of Blueberry Imprint Increasing Bacterial-Fungal Interkingdom Interactions along the Soil-Rhizosphere-Root Continuum.

Plant root-associated microbiomes play critical roles in promoting plant health, productivity, and tolerance to biotic/abiotic stresses. Blueberry (Vaccinium spp.) is adapted to acidic soils, while the interactions of the root-associated microbiomes in this specific habitat under various root microenvironments remain elusive. Here, we investigated the diversity and community composition of bacterial and fungal communities in various blueberry root niches (bulk soil, rhizosphere soil, and root endosphere). The results showed that blueberry root niches significantly affected root-associated microbiome diversity and community composition compared to those of the three host cultivars. Deterministic processes gradually increased along the soil-rhizosphere-root continuum in both bacterial and fungal communities. The co-occurrence network topological features showed that both bacterial and fungal community complexity and intensive interactions decreased along the soil-rhizosphere-root continuum. Different compartment niches clearly influenced bacterial-fungal interkingdom interactions, which were significantly higher in the rhizosphere, and positive interactions gradually dominated the co-occurrence networks from the bulk soil to the endosphere. The functional predictions showed that rhizosphere bacterial and fungal communities may have higher cellulolysis and saprotrophy capacities, respectively. Collectively, the root niches not only affected microbial diversity and community composition but also enhanced the positive interkingdom interactions between bacterial and fungal communities along the soil-rhizosphere-root continuum. This provides an essential basis for manipulating synthetic microbial communities for sustainable agriculture. IMPORTANCE The blueberry root-associated microbiome plays an essential role in its adaptation to acidic soils and in limiting the uptake of soil nutrients by its poor root system. Studies on the interactions of the root-associated microbiome in the various root niches may deepen our understanding of the beneficial effects in this particular habitat. Our study extended the research on the diversity and composition of microbial communities in different blueberry root compartment niches. Root niches dominated the root-associated microbiome compared to that of the host cultivar, and deterministic processes increased from the bulk soil to the endosphere. In addition, bacterial-fungal interkingdom interactions were significantly higher in the rhizosphere, and those positive interactions progressively dominated the co-occurrence network along the soil-rhizosphere-root continuum. Collectively, root niches dominantly affected the root-associated microbiome and the positive interkingdom interactions increased, potentially providing benefits for the blueberry.

Experimental study of the effects of absorbable gelatin sponge and non­absorbable polyvinyl alcohol particle material used in transcatheter arterial embolization on liver tissues.

Hepatic trauma is a leading cause of death in major abdominal trauma, and transcatheter arterial embolization has been widely used to treat it. However, there is limited research on whether absorbable gelatin sponge (AGS) and non-absorbable polyvinyl alcohol particles (PVA) have different effects on liver tissue, making it an important area of exploration. The present study investigated this issue using animal experiments by performing transhepatic arterial embolization with AGS and PVA. The effects on normal liver tissue in rabbits were examined by detecting liver function and inflammatory indexes, conducting histopathological examination, and using western blotting to detect apoptotic proteins. There were significant differences between the AGS and PVA groups after embolization. The AGS group exhibited a trend of improvement at ~1 week after embolization, and all indicators were statistically different until day 21 compared with the PVA group. The AGS group exhibited improved repair of hepatocytes and the biliary system based on H&E staining, while the PVA group exhibited more severe necrosis of the hepatocytes and biliary system around the embolization site. The western blotting results indicated that the Bcl-2/Bax ratio decreased on day 1 and day 3, and then rebounded in the AGS group on days 7 and 21, demonstrating gradual repair of hepatocytes compared with the PVA group.

Target Density Effects on Charge Transfer of Laser-Accelerated Carbon Ions in Dense Plasma.

We report on charge state measurements of laser-accelerated carbon ions in the energy range of several MeV penetrating a dense partially ionized plasma. The plasma was generated by irradiation of a foam target with laser-induced hohlraum radiation in the soft x-ray regime. We use the tricellulose acetate (C_{9}H_{16}O_{8}) foam of 2 mg/cm^{3} density and 1 mm interaction length as target material. This kind of plasma is advantageous for high-precision measurements, due to good uniformity and long lifetime compared to the ion pulse length and the interaction duration. We diagnose the plasma parameters to be T_{e}=17 eV and n_{e}=4×10^{20} cm^{-3}. We observe the average charge states passing through the plasma to be higher than those predicted by the commonly used semiempirical formula. Through solving the rate equations, we attribute the enhancement to the target density effects, which will increase the ionization rates on one hand and reduce the electron capture rates on the other hand. The underlying physics is actually the balancing of the lifetime of excited states versus the collisional frequency. In previous measurement with partially ionized plasma from gas discharge and z pinch to laser direct irradiation, no target density effects were ever demonstrated. For the first time, we are able to experimentally prove that target density effects start to play a significant role in plasma near the critical density of Nd-glass laser radiation. The finding is important for heavy ion beam driven high-energy-density physics and fast ignitions. The method provides a new approach to precisely address the beam-plasma interaction issues with high-intensity short-pulse lasers in dense plasma regimes.

Activating Wnt/ß-catenin signaling by autophagic degradation of APC contributes to the osteoblast differentiation effect of soy isoflavone on osteoporotic mesenchymal stem cells.

The functional role of autophagy in regulating differentiation of bone marrow mesenchymal stem cells (MSCs) has been studied extensively, but the underlying mechanism remains largely unknown. The Wnt/ß-catenin signaling pathway plays a pivotal role in the initiation of osteoblast differentiation of mesenchymal progenitor cells, and the stability of core protein ß-catenin is tightly controlled by the APC/Axin/GSK-3ß/Ck1α complex. Here we showed that genistein, a predominant soy isoflavone, stimulated osteoblast differentiation of MSCs in vivo and in vitro. Female rats were subjected to bilateral ovariectomy (OVX); four weeks after surgery the rats were orally administered genistein (50 mg·kg-1·d-1) for 8 weeks. The results showed that genistein administration significantly suppressed the bone loss and bone-fat imbalance, and stimulated bone formation in OVX rats. In vitro, genistein (10 nM) markedly activated autophagy and Wnt/ß-catenin signaling pathway, and stimulated osteoblast differentiation in OVX-MSCs. Furthermore, we found that genistein promoted autophagic degradation of adenomatous polyposis coli (APC), thus initiated ß-catenin-driven osteoblast differentiation. Notably, genistein activated autophagy through transcription factor EB (TFEB) rather than mammalian target of rapamycin (mTOR). These findings unveil the mechanism of how autophagy regulates osteogenesis in OVX-MSCs, which expands our understanding that such interplay could be employed as a useful therapeutic strategy for treating postmenopausal osteoporosis.

Comparison of preoperative ultrasound and MRI in the diagnosis of microvascular invasion in hepatocellular carcinoma.

Ultrasound has few reports on its application in prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). The purpose of this study was to explore the diagnostic efficacies of preoperative ultrasound and magnetic resonance imaging (MRI) for HCC MVI and compare these two imaging methods for the diagnosis of this condition. The clinical and preoperative ultrasound and MR imaging data of 26 patients with newly diagnosed HCC were collected between October 2020 and October 2021. According to the gold standard (postoperative pathology), the patients were divided into MVI-positive and MVI-negative groups, and the efficacies of ultrasound and MRI in diagnosing HCC MVI and the consistency between the two imaging modalities were analyzed. For the preoperative diagnosis of MVI using ultrasound, the sensitivity was 93.33%, the specificity was 81.82%, and the accuracy was 88.46%. For preoperative MRI, the sensitivity was 66.67%, the specificity was 100%, and the accuracy was 80.77%. In diagnosing MVI, the two methods had significantly different efficacy (P = 0.031). Ultrasound and MRI have high diagnostic efficiency for MVI, but the accuracy of preoperative MRI was lower than that of preoperative ultrasound. These results indicate that ultrasound has a certain guiding significance in the diagnosis of HCC MVI.

Transport of dimethyl phthalate on loess with modified bentonite: A batch and column test investigation.

Phthalic acid ester (PAE) is a toxic pollutant commonly found in high concentrations in municipal solid waste landfills. Soil-bentonite is widely used as a barrier material to control groundwater contaminants from landfill leachates. Traditional soil-bentonite materials always have a limited capacity for organic pollutant adsorption. To address this issue, the adsorption and transport behavior of dimethyl phthalate (DMP) on loess amended with two kinds of modified bentonite (HTMAC-B, modified with hexadecyltrimethylammonium chloride; CMC-B, modified with hydrophobic cationic surfactant, and carboxymethyl cellulose) were investigated. The kinetics of DMP adsorption indicates that film diffusion contributes significantly to the kinetic adsorption of DMP on HTMAC-B. The adsorption isotherm results showed that partitioning dominated DMP adsorption on loess with both modified bentonites. Owing to the in-ionic sites in HTMAC-B, which attracted hydrophobic compounds such as DMP, the adsorption capacity of 5 % HTMAC-B-amended loess (LH) was increased by a factor of 3.2. However, because CMC-B provided mostly ionic sites, 5 % CMC-B-amended loess (LC) had a little effect on DMP adsorption. The hydraulic conductivity values of LH and LC were 5.95 × 10-10 and 1.65 × 10-11 m/s, respectively. The X-CT result showed that there is a significant porosity change for both LH and LC. Dual-porosity model reveals that the leaching process primarily affects micro-pores, rather than larger pores in the soil matrix. The predicted retardation factors for LH and LC were 38.89 and 9.67, respectively. When using loess-bentonite as barrier material, the amendment of HTMAC-B and CMC-B can help to increase the retardation ability and reduce the permeability, respectively.

Genistein mitigates senescence of bone marrow mesenchymal stem cells via ERRα-mediated mitochondrial biogenesis and mitophagy in ovariectomized rats.

Senescence of bone marrow mesenchymal stem cells (BMMSCs) induced by chronic oxidative stress is an important factor contributes to the postmenopausal osteoporosis (PMOP). Mitochondrial quality control takes a pivotal role in regulating oxidative stress and cell senescence. Genistein is a major isoflavone in soy products, which is best known for its ability to inhibit bone loss in both postmenopausal women and ovariectomized (OVX) rodents. Here we show that OVX-BMMSCs displayed premature senescence, elevated reactive oxygen species (ROS) level and mitochondria dysfunction, while genistein rescued these phenotypes. Using network pharmacology and molecular docking, we identified estrogen-related receptor α (ERRα) as the potential target of genistein. Knockdown of ERRα greatly abolished the anti-senescence effect of genistein on OVX-BMMSCs. Further, the mitochondrial biogenesis and mitophagy induced by genistein were inhibited by ERRα knockdown in OVX-BMMSCs. In vivo, genistein inhibited trabecular bone loss and p16INK4a expression, upregulated sirtuin 3 (SIRT3) and peroxisome proliferator-activated receptor gamma coactivator one alpha (PGC1α) expression in the trabecular bone area of proximal tibia in OVX rats. Together, this study revealed that genistein ameliorates senescence of OVX-BMMSCs through ERRα-mediated mitochondrial biogenesis and mitophagy, which provided a molecular basis for advancement and development of therapeutic strategies against PMOP.

Method validation of a bridging immunoassay in combination with acid-dissociation and bead treatment for detection of anti-drug antibody.

Anti-drug antibody (ADA) positivity is correlated with disease relapse risk when treated with monoclonal antibody (mAb) therapeutics. ADA evaluation can assist with interpreting pharmacokinetic, pharmacological, and toxicology results. Here, we established an ADA assay based on two steps of acid dissociation combined with a bridging immunoassay to provide a comprehensive validation strategy. The three-tiered sample analysis process included screening, confirmation, and titration assays using therapeutic HLX26 (targeting lymphocyte activation gene-3 [LAG-3]) as an example. The cut points were determined by testing 50 individual normal human serum samples, including screening cut point (SCP) (SNR: 1.08), confirmatory cut point (CCP) (% inhibition: 12.65), and titration cut point (TCP) (sample-to-noise ratio [SNR]: 1.17). The assay sensitivity, low positive control (LPC), and high positive control (HPC) titer acceptable range were also set up as 33.0 ng/mL, 41.0 ng/mL, and 320-1280, respectively. After full validation, both the intra-assay and inter-assay precision testing passed with coefficient of variations (CVs) < 20%. The assay enabled excellent drug tolerance up to 768.0 µg/mL at the HPC level and 291.0 µg/mL at the LPC level, while the tolerance of target interference was up to 74.0 ng/mL of soluble LAG3. Moreover, no false-positive results were observed in the presence of 5% hemolyzed serum samples and 150 mg/dL of triglyceride in the serum samples, no hook effect was observed, and the stability performed normally under room temperature for 24 h, 2-8 °C for 7 d, and six freeze/thaw cycles. In summary, this ADA assay is feasible and could be used for evaluating the immunogenicity of HLX26 in clinical trials.

Classification of Coronavirus Spike Proteins by Deep-Learning-Based Raman Spectroscopy and its Interpretative Analysis.

The outbreak of COVID-19 has spread worldwide, causing great damage to the global economy. Raman spectroscopy is expected to become a rapid and accurate method for the detection of coronavirus. A classification method of coronavirus spike proteins by Raman spectroscopy based on deep learning was implemented. A Raman spectra dataset of the spike proteins of five coronaviruses (including MERS-CoV, SARS-CoV, SARS-CoV-2, HCoVHKU1, and HCoV-OC43) was generated to establish the neural network model for classification. Even for rapidly acquired spectra with a low signal-to-noise ratio, the average accuracy exceeded 97%. An interpretive analysis of the classification results of the neural network was performed, which indicated that the differences in spectral characteristics captured by the neural network were consistent with the experimental analysis. The interpretative analysis method provided a valuable reference for identifying complex Raman spectra using deep-learning techniques. Our approach exhibited the potential to be applied in clinical practice to identify COVID-19 and other coronaviruses, and it can also be applied to other identification problems such as the identification of viruses or chemical agents, as well as in industrial areas such as oil and gas exploration.

Mechanical overloading induces GPX4-regulated chondrocyte ferroptosis in osteoarthritis via Piezo1 channel facilitated calcium influx.

INTRODUCTIONS: Excessive mechanical stress is closely associated with cell death in various conditions. Exposure of chondrocytes to excessive mechanical loading leads to a catabolic response as well as exaggerated cell death. Ferroptosis is a recently identified form of cell death during cell aging and degeneration. However, it's potential association with mechanical stress remains to be illustrated. OBJECTIVES: To identify whether excessive mechanical stress can cause ferroptosis. To explore the role of mechanical overloading in chondrocyte ferroptosis. METHODS: Chondrocytes were collected from loading and unloading zones of cartilage in patients with osteoarthritis (OA), and the ferroptosis phenotype was analyzed through transmission electron microscope and microarray. Moreover, the relationship between ferroptosis and OA was analyzed by GPX4-conditional knockout (Col2a1-CreERT: GPX4flox/flox) mice OA model and chondrocytes cultured with high strain mechanical stress. Furthermore, the role of Piezo1 ion channel in chondrocyte ferroptosis and OA development was explored by using its inhibitor (GsMTx4) and agonist (Yoda1). Additionally, chondrocyte was cultured in calcium-free medium with mechanical stress, and ferroptosis phenotype was tested. RESULTS: Human cartilage and mouse chondrocyte experiments revealed that mechanical overloading can induce GPX4-associated ferroptosis. Conditional knockout of GPX4 in cartilage aggravated experimental OA process, while additional treatment with ferroptosis suppressor protein (FSP-1) and coenzyme Q10 (CoQ10) abated OA development in GPX4-CKO mice. In mouse OA model and chondrocyte experiments, inhibition of Piezo1 channel activity increased GPX4 expression, attenuated ferroptosis phenotype and reduced the severity of osteoarthritis. Additionally, high strain mechanical stress induced ferroptosis damage in chondrocyte was largely abolished by blocking calcium influx through calcium-free medium. CONCLUSIONS: Our findings show that mechanical overloading induces ferroptosis through Piezo1 activation and subsequent calcium influx in chondrocytes, which might provide a potential target for OA treatment.

Long-term cultivation drives dynamic changes in the rhizosphere microbial community of blueberry.

Rhizosphere microbial communities profoundly affect plant health, productivity, and responses to environmental stress. Thus, it is of great significance to comprehensively understand the response of root-associated microbes to planting years and the complex interactions between plants and rhizosphere microbes under long-term cultivation. Therefore, four rabbiteye blueberries (Vaccinium ashei Reade) plantations established in 1988, 2004, 2013, and 2017 were selected to obtain the dynamic changes and assembly mechanisms of rhizosphere microbial communities with the increase in planting age. Rhizosphere bacterial and fungal community composition and diversity were determined using a high-throughput sequencing method. The results showed that the diversity and structure of bacterial and fungal communities in the rhizosphere of blueberries differed significantly among planting ages. A total of 926 operational taxonomic units (OTUs) in the bacterial community and 219 OTUs in the fungal community were identified as the core rhizosphere microbiome of blueberry. Linear discriminant analysis effect size (LEfSe) analysis revealed 36 and 56 distinct bacterial and fungal biomarkers, respectively. Topological features of co-occurrence network analysis showed greater complexity and more intense interactions in bacterial communities than in fungal communities. Soil pH is the main driver for shaping bacterial community structure, while available potassium is the main driver for shaping fungal community structure. In addition, the VPA results showed that edaphic factors and blueberry planting age contributed more to fungal community variations than bacterial community. Notably, ericoid mycorrhizal fungi were observed in cultivated blueberry varieties, with a marked increase in relative abundance with planting age, which may positively contribute to nutrient uptake and coping with environmental stress. Taken together, our study provides a basis for manipulating rhizosphere microbial communities to improve the sustainability of agricultural production during long-term cultivation.