A Phase I Clinical Study Comparing the Pharmacokinetics, Safety, and Immunogenicity of GB221 Injection and Trastuzumab (Herceptin®) in Healthy Chinese Adults.

BACKGROUND AND OBJECTIVE: GB221 is a recombinant humanized anti-HER2 monoclonal antibody. The purpose of this study was to evaluate the pharmacokinetic, safety, and immunogenicity of GB221 in healthy Chinese adults in comparison to trastuzumab (Herceptin®). METHODS: In this randomized, double-blind, parallel-group phase I clinical trial, 88 subjects were randomized 1:1 to receive a single intravenous infusion (90-100 min) of GB221 or trastuzumab (6 mg/kg). The primary pharmacokinetic parameters-maximum observed serum concentration (Cmax), area under the serum concentration-time curve from zero to the last quantifiable concentration at time t (AUC0-t), and area under the serum concentration-time curve from time zero to infinity (AUC0-∞)-of GB221 and trastuzumab were compared to establish whether the 90% confidence interval (CI) attained the 80-125% bioequivalence standard. Safety and immunogenicity were also evaluated. RESULTS: The GB221 group (n = 43) and the trastuzumab group (n = 44) showed similar pharmacokinetic characteristics. The geometric mean ratios (90% CI) of Cmax, AUC0-t, and AUC0-∞ between the two groups were 107.53% (102.25-113.07%), 108.31% (103.57-113.26%), and 108.34% (103.57-113.33%), respectively. The incidence of treatment-emergent adverse events (TEAEs) was 83.7% (36/43) of the subjects in the GB221 group and 95.5% (42/44) of the subjects in the trastuzumab group. No subjects withdrew from the trial due to TEAEs, and there were no occurrences of serious adverse events. All subjects tested negative for antidrug antibodies (ADA). CONCLUSION: GB221 demonstrated similar pharmacokinetics to trastuzumab and comparable safety and immunogenicity in healthy Chinese adults.

A dynamic regulatory switch for phase separation of FUS protein: Zinc ions and zinc finger domain.

Zinc is an important trace element in the human body, and its homeostasis is closely related to amyotrophic lateral sclerosis (ALS). Cytoplasmic FUS proteins from patients with ALS aggregate their important pathologic markers. Liquid-liquid phase separation (LLPS) of FUS can lead to its aggregation. However, whether and how zinc homeostasis affects the aggregation of disease-associated FUS proteins in the cytoplasm remains unclear. Here, we found that zinc ion enhances LLPS and promotes the aggregation in the cytoplasm for FUS protein. In the FUS, the cysteine of the zinc finger (ZnF), recognizes and binds to zinc ions, reducing droplet mobility and enhancing protein aggregation in the cytoplasm. The mutation of FUS cysteine disrupts the dynamic regulatory switch of zinc ions and ZnF, resulting in insensitivity to zinc ions. These results suggest that the dynamic regulation of LLPS by binding with zinc ions may be a widespread mechanism and provide a new understanding of neurological diseases such as ALS and other ZnF protein-related diseases.

B(C6F5)3/Chiral Phosphoric Acid Catalyzed Asymmetric Aza-Diels-Alder Reaction of Imines and Unactivated Dienes.

Herein, we report an asymmetric aza-Diels-Alder reaction of quinoxalinones or benzoxazinones with unactivated dienes by utilizing a B(C6F5)3/chiral phosphoric acid catalyst to construct chiral six-membered N-heterocycles. Various quinoxalinones or benzoxazinones with electron-withdrawing and electron-donating groups and unactivated dienes were tolerated (up to 99% yield and 99% ee) in the methodology with only 2 mol % catalyst loading. Moreover, the luminescence mechanism and photophysical properties of the product were tested and used for anticounterfeiting of QR codes.

Flexible Aerogel Materials: A Review on Revolutionary Flexibility Strategies and the Multifunctional Applications.

The design and preparation of flexible aerogel materials with high deformability and versatility have become an emerging research topic in the aerogel fields, as the brittle nature of traditional aerogels severely affects their safety and reliability in use. Herein, we review the preparation methods and properties of flexible aerogels and summarize the various controlling and design methods of aerogels to overcome the fragility caused by high porosity and nanoporous network structure. The mechanical flexibility of aerogels can be revolutionarily improved by monomer regulation, nanofiber assembly, structural design and controlling, and constructing of aerogel composites, which can greatly broaden the multifunctionality and practical application prospects. The design and construction criterion of aerogel flexibility is summarized: constructing a flexible and deformable microstructure in an aerogel matrix. Besides, the derived multifunctional applications in the fields of flexible thermal insulation (flexible thermal protection at extreme temperatures), flexible wearable electronics (flexible sensors, flexible electrodes, electromagnetic shielding, and wave absorption), and environmental protection (oil/water separation and air filtration) are summarized. Furthermore, the future development prospects and challenges of flexible aerogel materials are also summarized. This review will provide a comprehensive research basis and guidance for the structural design, fabrication methods, and potential applications of flexible aerogels.

A multi-scale attention residual-based U-Net network for stroke electrical impedance tomography.

Electrical impedance tomography (EIT), a non-invasive, radiation-free, and convenient imaging technique, has been widely used in the diagnosis of stroke. However, due to soft-field nonlinearity and the ill-posed inverse problem, EIT images always suffer from low spatial resolution. Therefore, a multi-scale convolutional attention residual-based U-Net (MARU-Net) network is proposed for stroke reconstruction. Based on the U-Net network, a residual module and a multi-scale convolutional attention module are added to the concatenation layer. The multi-scale module extracts feature information of different sizes, the attention module strengthens the useful information, and the residual module improves the performance of the network. Based on the above advantages, the network is used in the EIT system for stroke imaging. Compared with convolutional neural networks and one-dimensional convolutional neural networks, the MARU-Net network has fewer artifacts, and the reconstructed image is clear. At the same time, the reduction of noisy artifacts in the MARU-Net network is verified. The results show that the image correlation coefficient of the reconstructed image with noise is greater than 0.87. Finally, the practicability of the network is verified by a model physics experiment.

p53 accelerates endothelial cell senescence in diabetic retinopathy by enhancing FoxO3a ubiquitylation and degradation via UBE2L6.

Diabetic retinopathy (DR) is the most common ocular fundus disease in diabetic patients. Chronic hyperglycemia not only promotes the development of diabetes and its complications, but also aggravates the occurrence of senescence. Previous studies have shown that DR is associated with senescence, but the specific mechanism has not been fully elucidated. Here, we first detected the differentially expressed genes (DEGs) and cellular senescence level of db/db mouse retinas by bulk RNA sequencing. Then, we used single-cell sequencing (scRNA-seq) to identify the main cell types in the retina and analyzed the DEGs in each cluster. We demonstrated that p53 expression was significantly increased in retinal endothelial cell cluster of db/db mice. Inhibition of p53 can reduce the expression of SA-ß-Gal and the senescence-associated secretory phenotype (SASP) in HRMECs. Finally, we found that p53 can promote FoxO3a ubiquitination and degradation by increasing the expression of the ubiquitin-conjugating enzyme UBE2L6. Overall, our results demonstrate that p53 can accelerate the senescence process of endothelial cells and aggravate the development of DR. These data reveal new targets and insights that may be used to treat DR.

CKR-1 orchestrates two motor states from a single motoneuron in C. elegans.

Neuromodulation is pivotal in modifying neuronal properties and motor states. CKR-1, a homolog of the cholecystokinin receptor, modulates robust escape steering and undulation body bending in C. elegans. Nevertheless, the mechanisms through which CKR-1 governs these motor states remain elusive. We elucidate the head motoneuron SMD as the orchestrator of both motor states. This regulation involves two neuropeptides: NLP-12 from DVA enhances undulation body curvature, while NLP-18 from ASI amplifies Ω-turn head curvature. Moreover, synthetic NLP-12 and NLP-18 peptides elicit CKR-1-dependent currents in Xenopus oocytes and Ca2+ transients in SMD neurons. Notably, CKR-1 shows higher sensitivity to NLP-18 compared to NLP-12. In situ patch-clamp recordings reveal CKR-1, NLP-12, and NLP-18 are not essential for neurotransmission at C. elegans neuromuscular junction, suggesting that SMD independently regulates head and body bending. Our studies illustrate that a single motoneuron SMD utilizes a cholecystokinin receptor CKR-1 to integrate two motor states.

Differential intestinal effects of water and foodborne exposures of nano-TiO2 in the mussel Mytilus coruscus under elevated temperature.

With the wide use of nanomaterials in daily life, nano-titanium dioxide (nano-TiO2) presents potential ecological risks to marine ecosystems, which can be exacerbated by ocean warming (OW). However, most previous studies have only centered around waterborne exposure, while there is a scarcity of studies concentrating on the impact of trophic transfer exposure on organisms. We investigated the differences in toxic effects of 100 µg/L nano-TiO2 on mussels via two pathways (waterborne and foodborne) under normal (24 °C) and warming (28 °C) conditions. Single nano-TiO2 exposure (waterborne and foodborne) elevated the superoxide dismutase (SOD) and catalase (CAT) activities as well as the content of glutathione (GSH), indicating activated antioxidatant response in the intestine. However, depressed antioxidant enzymes and accumulated peroxide products (LPO and protein carbonyl content, PCC) demonstrated that warming in combination with nano-TiO2 broke the prooxidant-antioxidant homeostasis of mussels. Our findings also indicated that nano-TiO2 and high temperature exhibited adverse impacts on amylase (AMS), trypsin (PS), and trehalase (THL). Additionally, activated immune function (lysozyme) comes at the cost of energy expenditure of protein (decreased protein concentration). The hydrodynamic diameter of nano-TiO2 at 24 °C (1693-2261 nm) was lower than that at 28 °C (2666-3086 nm). Bioaccumulation results (range from 0.022 to 0.432 µg/g) suggested that foodborne induced higher Ti contents in intestine than waterborne. In general, the combined effects of nano-TiO2 and warming demonstrated a more pronounced extent of interactive effects and severe damage to antioxidant, digestive, and immune parameters in mussel intestine. The toxicological impact of nano-TiO2 was intensified through trophic transfer. The toxic effects of nano-TiO2 are non-negligible and can be exerted together through both water- and foodborne exposure routes, which deserves further investigation.

Expert consensus on irrigation and intracanal medication in root canal therapy.

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment. However, irrigant selection or irrigation procedures are far from clear. The vapor lock effect in the apical region has yet to be solved, impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes. Additionally, ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified. Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes. Indeed, clinicians have been aware of these concerns for years. Based on the current evidence of studies, this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions. The evolution of different kinetic irrigation methods, their effects, limitations, the paradigm shift, current indications, and effective operational procedures regarding intracanal medication are also discussed. This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication, thus facilitating a better understanding of infection control, standardizing clinical practice, and ultimately improving the success of endodontic therapy.

The impact of intellectual property rights protection on green innovation: A quasi-natural experiment based on the pilot policy of the Chinese intellectual property court.

In the context of high-quality economic development in China, it is important to promote green innovation development by protecting intellectual property rights (IPR). Taking the pilot policy of the intellectual property courts in Beijing, Shanghai, and Guangzhou for example in a quasi-natural experiment, this article examines the effect of IPR protection on the development of corporate green innovation and its mechanisms by using a difference-in-differences model and a mediating effect model based on Chinese enterprise data from 2011 to 2019. The study found that first, IPR protection promotes enterprise green technological innovation; second, IPR protection affects green innovation through enterprise financing constraints and R&D investment; that is, increasing enterprise R&D investment and alleviating enterprise financing constraints are two important channels through which IPR protection promotes enterprise green technological innovation.

Enantioselective C(sp2)-C(sp3) Bond Construction by Ni Catalysis.

ConspectusAfter decades of palladium dominating the realm of transition-metal-catalyzed cross-coupling, recent years have witnessed exciting advances in the development of new nickel-catalyzed cross-coupling reactions to form C(sp3) centers. Nickel possesses distinct properties compared with palladium, such as facile single-electron transfer to C(sp3) electrophiles and rapid C-C reductive elimination from NiIII. These properties, among others, make nickel particularly well-suited for reductive cross-coupling (RCC) in which two electrophiles are coupled and an exogenous reductant is used to turn over the metal catalyst. Ni-catalyzed RCCs use readily available and stable electrophiles as starting materials and exhibit good functional group tolerance, which makes them appealing for applications in the synthesis of complex molecules. Building upon the foundational work in Ni-catalyzed RCCs by the groups of Kumada, Durandetti, Weix, and others, as well as the advancements in Ni-catalyzed enantioselective redox-neutral cross-couplings led by Fu and co-workers, we initiated a program to explore the feasibility of developing highly enantioselective Ni-catalyzed RCCs. Our research has also been driven by a keen interest in unraveling the factors contributing to enantioinduction and electrophile activation as we seek new avenues for advancing our understanding and further developing these reactions.In the first part of this Account, we organize our reported methods on the basis of the identity of the C(sp3) electrophiles, including benzylic chlorides, N-hydroxyphthalimide (NHP) esters, and α-chloro esters and nitriles. We highlight how the selection of specific chiral ligands plays a pivotal role in achieving high cross-selectivity and enantioselectivity. In addition, we show that reduction can be accomplished not only with heterogeneous reductants, such as Mn0, but also with the soluble organic reductant tetrakis(dimethylamino)ethylene (TDAE), as well as electrochemically. The use of homogeneous reductants, such as TDAE, is well suited for studying the mechanism of the transformation. Although this Account primarily focuses on RCCs, we also highlight our work using trifluoroborate (BF3K) salts as radical precursors for enantioselective dual-Ni/photoredox systems.At the end of this Account, we summarize the relevant mechanistic studies of two closely related asymmetric reductive alkenylation reactions developed in our laboratory and provide a context between our work and related mechanistic studies by others. We discuss how the ligand properties influence the rates and mechanisms of electrophile activation and how understanding the mode of C(sp3) radical generation can be used to optimize the yield of an RCC. Our research endeavors to offer insights on the intricate mechanisms at play in asymmetric Ni-catalyzed RCCs with the goal of using the rate of electrophile activation to improve the substrate scope of enantioselective RCCs. We anticipate that the insights we share in this Account can provide guidance for the development of new methods in this field.

Multifunctional Fe-S bonds assist poly(3,4-ethylenedioxythiophene) to enhance iron diselenide for ultra-long sodium storage lifetime.

Transition metal selenides (TMS) have been used to prepare hundreds of electrode materials for ion batteries due to their superior theoretical capacity, but have been repeatedly limited by the sluggish reaction kinetics and the enormous volume change during the repeated charge/discharge process. Here, we report a facile strategy to fabricate organic-inorganic composites by engineering a unique chemical bonding interface between TMS and conductive polymers. For the first time, poly(3,4-ethylenedioxythiophene) (PEDOT) is utilized to encapsulate iron diselenide (FeSe2) nanoparticles by in situ polymerization, and the Fe-S bonds are meanwhile formed at the interface of FeSe2 and PEDOT. The experimental analysis demonstrates the stability of Fe-S bonds during the sodiation/desodiation process and after long cycling, which can serve as a "bridge" for fast charge transfer and also serve as a "rivet" to stabilize the composite structure. When used for sodium ion storage, the composite offers an exceptionally long lifetime of up to 17,000 loops at 10 A/g without capacity degradation. In addition, it delivers a high specific capacity of 490.4 mAh/g and retains 60 % when the current density is amplified 150 times. The assembled full cell also exhibits excellent cycling stability. This work will provide a feasible way to improve the metal oxide/sulfide/selenides for long-life ion batteries.

A pilot study of [68Ga]Ga-fibroblast activation protein inhibitor-04 PET/CT in renal cell carcinoma.

OBJECTIVES: As a promising positron emission tomography (PET) tracer, [68Ga]Ga-fibroblast activation protein inhibitor-04([68Ga]Ga-FAPI-04) performs better than 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) at diagnosing primary and metastatic lesions in patients with various types of cancer. We investigated the utility of [68Ga]Ga-FAPI-04 PET/CT for the detection of primary and metastatic lesions in renal cell carcinoma (RCC). [18F]FDG PET/CT were used for comparison. METHODS: Twenty-two patients with suspected RCC or recurrent RCC were enrolled in our study. Among these patients, 14 were newly diagnosed with RCC, 3 had recurrent RCC, and 5 were excluded from further analysis due to having benign renal tumours. Seventeen patients with RCC underwent [68Ga]Ga-FAPI-04 PET/CT, and 6 of them also received [18F]FDG PET/CT. The positive detection rates were calculated and compared with those in patients who underwent both scans. RESULTS: Data from 17 patients with RCC (median age: 60.5 years, interquartile range [IQR]: 54-70 years) were evaluated. The positive detection rate of [68Ga]Ga-FAPI-04 PET/CT for RCC was 64.7% (11/17). Lymph node metastases (n = 44), lung metastasis (n = 1), and bone metastasis (n = 1) were detected. Six patients with RCC underwent [68Ga]Ga-FAPI-04 and [18F]FDG PET/CT. [68Ga]Ga-FAPI-04 PET/CT showed a higher positive detection rate than [18F]FDG PET/CT in detecting RCC (83.3% [5/6] vs. 50% [3/6], P = 0.545). Additionally, [68Ga]Ga-FAPI-04 PET/CT has higher SUVmax (3.20 [IQR: 2.91-5.80 vs. 2.71 [IQR: 2.13-3.10], P = 0.116) and tumour-to-background ratio (TBR) values (1.60 [IQR: 1.33-3.67] vs. 0.86 [0.48-1.21], P = 0.028) than [18F]FDG PET/CT. CONCLUSIONS: These findings suggest that [68Ga]Ga-FAPI-04 PET/CT has potential value in RCC diagnosis. Further studies are warranted to validate these results. ADVANCES IN KNOWLEDGE: Clinical utility of [68Ga]Ga-FAPI-04 in RCC remains unclear, and there are not many similar studies in the literature. We evaluated the role of [68Ga]Ga-FAPI-04 in diagnosing RCC.

Exosomes Derived from Quercetin-Treated Bone Marrow Derived Mesenchymal Stem Cells Inhibit the Progression of Osteoarthritis Through Delivering miR-124-3p to Chondrocytes.

Osteoarthritis (OA) is a chronic disease characterized by the progressive loss of cartilage and failure of the diarrheal joint. Quercetin has been reported to attenuate the development of OA. Bone marrow derived mesenchymal stem cell (BMSC)-derived exosomes are involved in OA progression. However, the role of BMSC-derived exosomes in quercetin-mediated progression of OA remains unclear. Western blotting and RT-qPCR were used to assess protein and mRNA levels, respectively. CCK8 assay was performed to assess cell viability, and cell apoptosis was assessed using flow cytometry. A dual-luciferase assay was performed to assess the relationship between miR-124-3p and TRAF6 expression. Furthermore, in vivo experiments were performed to test the function of exosomes derived from Quercetin-treated BMSCs in OA patients. IL-1ß significantly inhibited the viability of chondrocytes, whereas the conditioned medium of Quercetin-treated BMSCs (BMSCsQUE-CM) reversed this phenomenon through exosomes. IL-1ß notably upregulated MMP13 and ADAMT5 and reduced the expression of COL2A1 in chondrocytes, which were rescued by BMSCsQUE-CM. The effects of BMSCsQUE-CM on these three proteins were reversed in the absence of exosomes. Exosomes can be transferred from BMSCs to chondrocytes, and exosomes derived from Quercetin-treated BMSCs (BMSCsQue-Exo) can reverse the apoptotic effects of IL-1ß on chondrocytes. The level of miR-124-3p in BMSCs was significantly upregulated by quercetin, and miR-124-3p was enriched in BMSCsQue-Exo. TRAF6 was identified as a direct target of miR-124-3p, and BMSCsQue-Exo abolished the IL-1ß-induced activation of MAPK/p38 and NF-κB signaling. Furthermore, BMSCsQue-Exo significantly attenuated OA progression in vivo. Exosomes derived from Quercetin-treated BMSCs inhibited OA progression through the upregulation of miR-124-3p.

Wearable Sensors for Breath Monitoring Based on Water-Based Hexagonal Boron Nitride Inks Made with Supramolecular Functionalization.

Wearable humidity sensors are attracting strong attention as they allow for real-time and continuous monitoring of important physiological information by enabling activity tracking as well as air quality assessment. Amongst 2Dimensional (2D) materials, graphene oxide (GO) is very attractive for humidity sensing due to its tuneable surface chemistry, high surface area, processability in water, and easy integration onto flexible substrates. However, strong hysteresis, low sensitivity, and cross-sensitivity issues limit the use of GO in practical applications, where continuous monitoring is preferred. Herein, a wearable and wireless impedance-based humidity sensor made with pyrene-functionalized hexagonal boron nitride (h-BN) nanosheets is demonstrated. The device shows enhanced sensitivity towards relative humidity (RH) (>1010 Ohms/%RH in the range from 5% to 100% RH), fast response (0.1 ms), no appreciable hysteresis, and no cross-sensitivity with temperature in the range of 25-60 °C. The h-BN-based sensor is able to monitor the whole breathing cycle process of exhaling and inhaling, hence enabling to record in real-time the subtlest changes of respiratory signals associated with different daily activities as well as various symptoms of flu, without requiring any direct contact with the individual.

The dropper stress characteristics under different moving load speeds for a high-speed railway.

Dropper failure seriously threatens the operation safety of a high-speed railway. In this work, for a simple chain suspension catenary, one span with five droppers is performed to establish a model and thus the effects of the moving load speed on dropper stress are investigated. First, the partial differential vibration equation of dropper is obtained through the mechanical analysis and converted into the finite difference equation. Then, we consider contact line as a beam element to obtain its motion equation. Furthermore, the boundary and initial conditions of five droppers are determined. Finally, the stresses of five droppers are numerically calculated and the effects of the moving load speed on dropper stress are investigated by writing a MATLAB code. The results suggest that the dropper location significantly affects its stress. Compared with other droppers, droppers II and IV have much more severe vibration amplitudes. Different moving load speeds could cause different stress change of each dropper. With the increasing speed, dropper experiences longer bending compression stage and the bending amplitude increases. The impact of the moving load speed on dropper stress is significant.

Endothelial YAP Mediates Hyperglycemia-Induced Platelet Hyperactivity and Arterial Thrombosis.

BACKGROUND: Hyperglycemia-a symptom that characterizes diabetes-is highly associated with atherothrombotic complications. However, the underlying mechanism by which hyperglycemia fuels platelet activation and arterial thrombus formation is still not fully understood. METHODS: The profiles of polyunsaturated fatty acid metabolites in the plasma of patients with diabetes and healthy controls were determined with targeted metabolomics. FeCl3-induced carotid injury model was used to assess arterial thrombus formation in mice with endothelial cell (EC)-specific YAP (yes-associated protein) deletion or overexpression. Flow cytometry and clot retraction assay were used to evaluate platelet activation. RNA sequencing and multiple biochemical analyses were conducted to unravel the underlying mechanism. RESULTS: The plasma PGE2 (prostaglandin E2) concentration was elevated in patients with diabetes with thrombotic complications and positively correlated with platelet activation. The PGE2 synthetases COX-2 (cyclooxygenase-2) and mPGES-1 (microsomal prostaglandin E synthase-1) were found to be highly expressed in ECs but not in other type of vessel cells in arteries from both patients with diabetes and hyperglycemic mice, compared with nondiabetic individuals and control mice, respectively. A combination of RNA sequencing and ingenuity pathway analyses indicated the involvement of YAP signaling. EC-specific deletion of YAP limited platelet activation and arterial thrombosis in hyperglycemic mice, whereas EC-specific overexpression of YAP in mice mimicked the prothrombotic state of diabetes, without affecting hemostasis. Mechanistically, we found that hyperglycemia/high glucose-induced endothelial YAP nuclear translocation and subsequently transcriptional expression of COX-2 and mPGES-1 contributed to the elevation of PGE2 and platelet activation. Blockade of EP3 (prostaglandin E receptor 3) activation by oral administration of DG-041 reversed the hyperactivity of platelets and delayed thrombus formation in both EC-specific YAP-overexpressing and hyperglycemic mice. CONCLUSIONS: Collectively, our data suggest that hyperglycemia-induced endothelial YAP activation aggravates platelet activation and arterial thrombus formation via PGE2/EP3 signaling. Targeting EP3 with DG-041 might be therapeutic for diabetes-related thrombosis.

Ocular Biometric Characteristics in Preoperative Diagnosis of Acute Angle Closure With and Without Zonular Laxity.

PRCIS: Biometric parameters, including binocular difference of anterior chamber depth (ACD), lens vault (LV) in affected eyes, and binocular difference of the LV, had high efficiency in diagnosing acute angle closure (AAC) with zonular laxity. PURPOSE: To investigate the ocular biometric characteristics of eyes with AAC with zonular laxity to further explore the sensitive parameters for preoperative diagnosis. METHODS: This study included 50 patients with AAC with zonular laxity and 54 patients with AAC without zonular laxity. Demographic data, ocular examination results, and biometric parameters on ultrasound biomicroscopy images were compared between the affected and fellow eyes in 2 groups. Parameters significant in the multiple linear regression model were included in a regression equation and the diagnostic efficiency was evaluated by area under the curve. RESULTS: In patients with AAC with zonular laxity, the binocular difference of central ACD, LV in affected eyes, and binocular difference of the LV were significantly larger than those in patients without zonular laxity respectively and these three parameters were all significant in multiple linear regression analysis (all P <0.001). The area under the curve of binocular difference of ACD, LV in affected eyes, and binocular difference of LV were 0.972, 0.796, and 0.855, respectively, with the cutoff values of 0.23, 1.28, and 0.19 mm. The regression equation containing these three parameters was: ln ( P /(1- P ))=-4.322 + 1.222 [LV in affected eyes (mm)] + 3.657 [binocular difference of LV (mm)] + 6.542 [binocular difference of ACD (mm)], with the accuracy of prediction reaching 94.05%. CONCLUSION: Binocular difference of ACD, LV in affected eyes, and binocular difference of LV had high efficiency in diagnosing AAC with zonular laxity.

The combined effects of phenanthrene and micro-/nanoplastics mixtures on the cellular stress responses of the thick-shell mussel Mytilus coruscus.

Pollution with complex mixtures of contaminants including micro- and nano-plastics (MNPs) and organic pollutants like polycyclic aromatic hydrocarbons (PAH) poses a major threat to coastal marine ecosystems. Toxic mechanisms of contaminant mixtures are not well understood in marine organisms. We studied the effects of single and combined exposures to polycyclic aromatic hydrocarbon phenanthrene (Phe) and MNPs mixture with sizes of 70 nm, 5 µm and 100 µm on the immune health and oxidative stress parameters in the thick-shell mussel Mytilus coruscus. Immune cells (hemocytes) were more sensitive to the pollutant-induced oxidative stress than the gills. In hemocytes of co-exposed mussels, elevated mortality, lower lysosomal content, high production of reactive oxygen species (ROS) and decrease mitochondrial were found. Disparate responses of antioxidant enzymes in the hemolymph (e.g. increased superoxide dismutase (SOD) activity without a corresponding increase in catalase (CAT) in Phe exposures and an increase in CAT without a change in SOD in MNPs exposures) suggests misbalance of the antioxidant defense in the pollutant-exposed mussels. Gill lacked pronounced oxidative stress response showing a decline in ROS and antioxidant levels. Tissue-specific single and combined effects of Phe and MNPs suggest variation in bioavailability and/or different sensitivity to these pollutants in the studied tissues. Notably, the combined effects of MNPs and Phe were additive or antagonistic, showing that MNPs do not enhance and occasionally mitigate the toxic effects of Phe on the hemocytes and the gills of the mussels. Overall, our study sheds light on the impact of long-term exposure to MNPs and Phe mixtures on mussels, showing high sensitivity of the immune system and modulation of the Phe toxicity by MNPs co-exposure. These findings that may have implications for understanding the impacts of combined PAH and MNPs pollution on the health of mussel populations from polluted coastal habitats.

Regulation of SiO2 Nanoparticles on the Adsorptive Fractionation of Dissolved Organic Matter by Goethite.

SiO2 nanoparticles (SiO2NPs) are most widely available and coexisting with DOM at the mineral-water interface; however, the role of SiO2NPs in DOM fractionation and the underlying mechanisms have not been fully understood. Using Fourier transform ion cyclotron resonance mass spectrometry, combined with Fourier transform infrared spectroscopy and X-ray adsorption fine structure spectroscopy, was employed to investigate the adsorptive fractionation of litter layer-derived DOM on goethite coexisting with SiO2NPs under different pH conditions. Results indicated that the inhibitory effect of the coexisting SiO2NPs on OM sorbed by goethite was waning as environmental pH increased due to the reduced steric interactions and the concurrent elevated hydrogen bonding/hydrophobic partitioning interactions on the goethite surface. We observed the coexisting SiO2NPs inhibited the adsorption of high carboxylic-containing condensed aromatic/aromatics compounds on goethite under different pH conditions while improving the adsorption of highly unsaturated aliphatic/phenolic and carbohydrate-like compounds in an alkaline and/or circumneutral environment. More nitrogen-containing structures may favor the adsorption of phenolic and nonaromatic compounds to goethite by counteracting the negative effect of SiO2NPs. These findings suggest that DOM sequestration may be significantly regulated by the coexisting SiO2NPs at the mineral-water interface, which may further influence the carbon-nitrogen cycling and contaminant fate in natural environments.