Intravital Microscopy Reveals Unforeseen Biodistribution Within the Liver and Kidney Mechanistically Connected to the Clearance of a Bifunctional Antibody.

Bifunctional antibody (BfAb) therapeutics offer the potential for novel functionalities beyond those of the individual monospecific entities. However, combining these entities into a single molecule can have unpredictable effects, including changes in pharmacokinetics that limit the compound's therapeutic profile. A better understanding of how molecular modifications affect in vivo tissue interactions could help inform BfAb design. The present studies were predicated on the observation that a BfAb designed to have minimal off-target interactions cleared from the circulation twice as fast as the monoclonal antibody (mAb) from which it was derived. The present study leverages the spatial and temporal resolution of intravital microscopy (IVM) to identify cellular interactions that may explain the different pharmacokinetics of the two compounds. Disposition studies of mice demonstrated that radiolabeled compounds distributed similarly over the first 24 hours, except that BfAb accumulated approximately two- to -three times more than mAb in the liver. IVM studies of mice demonstrated that both distributed to endosomes of liver endothelia but with different kinetics. Whereas mAb accumulated rapidly within the first hour of administration, BfAb accumulated only modestly during the first hour but continued to accumulate over 24 hours, ultimately reaching levels similar to those of the mAb. Although neither compound was freely filtered by the mouse or rat kidney, BfAb, but not mAb, was found to accumulate over 24 hours in endosomes of proximal tubule cells. These studies demonstrate how IVM can be used as a tool in drug design, revealing unpredicted cellular interactions that are undetectable by conventional analyses. SIGNIFICANCE STATEMENT: Bifunctional antibodies offer novel therapeutic functionalities beyond those of the individual monospecific entities. However, combining these entities into a single molecule can have unpredictable effects, including undesirable changes in pharmacokinetics. Studies of the dynamic distribution of a bifunctional antibody and its parent monoclonal antibody presented here demonstrate how intravital microscopy can expand our understanding of the in vivo disposition of therapeutics, detecting off-target interactions that could not be detected by conventional pharmacokinetics approaches or predicted by conventional physicochemical analyses.

SlTDC1 Overexpression Promoted Photosynthesis in Tomato under Chilling Stress by Improving CO2 Assimilation and Alleviating Photoinhibition.

Chilling causes a significant decline in photosynthesis in tomato plants. Tomato tryptophan decarboxylase gene 1 (SlTDC1) is the first rate-limiting gene for melatonin (MT) biosynthesis and is involved in the regulation of photosynthesis under various abiotic stresses. However, it is not clear whether SlTDC1 participates in the photosynthesis of tomato under chilling stress. Here, we obtained SlTDC1 overexpression transgenic tomato seedlings, which showed higher SlTDC1 mRNA abundance and MT content compared with the wild type (WT). The results showed that the overexpression of SlTDC1 obviously alleviated the chilling damage to seedlings in terms of the lower electrolyte leakage rate and hydrogen peroxide content, compared with the WT after 2 d of chilling stress. Moreover, the overexpression of SlTDC1 notably increased photosynthesis under chilling stress, which was related to the higher chlorophyll content, normal chloroplast structure, and higher mRNA abundance and protein level of Rubisco and RCA, as well as the higher carbon metabolic capacity, compared to the WT. In addition, we found that SlTDC1-overexpressing seedlings showed higher Wk (damage degree of OEC on the PSII donor side), φEo (quantum yield for electron transport in the PSII reaction center), and PIABS (photosynthetic performance index) than WT seedlings after low-temperature stress, implying that the overexpression of SlTDC1 decreased the damage to the reaction center and donor-side and receptor-side electron transport of PSII and promoted PSI activity, as well as energy absorption and distribution, to relieve the photoinhibition induced by chilling stress. Our results support the notion that SlTDC1 plays a vital role in the regulation of photosynthesis under chilling stress.

Abscisic Acid Mediates Salicylic Acid Induced Chilling Tolerance of Grafted Cucumber by Activating H2O2 Biosynthesis and Accumulation.

Grafting is widely applied to enhance the tolerance of some vegetables to biotic and abiotic stress. Salicylic acid (SA) is known to be involved in grafting-induced chilling tolerance in cucumber. Here, we revealed that grafting with pumpkin (Cucurbita moschata, Cm) as a rootstock improved chilling tolerance and increased the accumulation of SA, abscisic acid (ABA) and hydrogen peroxide (H2O2) in grafted cucumber (Cucumis sativus/Cucurbita moschata, Cs/Cm) leaves. Exogenous SA improved the chilling tolerance and increased the accumulation of ABA and H2O2 and the mRNA abundances of CBF1, COR47, NCED, and RBOH1. However, 2-aminoindan-2-phosphonic acid (AIP) and L-a-aminooxy-b-phenylpropionic acid (AOPP) (biosynthesis inhibitors of SA) reduced grafting-induced chilling tolerance, as well as the synthesis of ABA and H2O2, in cucumber leaves. ABA significantly increased endogenous H2O2 production and the resistance to chilling stress, as proven by the lower electrolyte leakage (EL) and chilling injury index (CI). However, application of the ABA biosynthesis inhibitors sodium tungstate (Na2WO4) and fluridone (Flu) abolished grafting or SA-induced H2O2 accumulation and chilling tolerance. SA-induced plant response to chilling stress was also eliminated by N,N'-dimethylthiourea (DMTU, an H2O2 scavenger). In addition, ABA-induced chilling tolerance was attenuated by DMTU and diphenyleneiodonium (DPI, an H2O2 inhibitor) chloride, but AIP and AOPP had little effect on the ABA-induced mitigation of chilling stress. Na2WO4 and Flu diminished grafting- or SA-induced H2O2 biosynthesis, but DMTU and DPI did not affect ABA production induced by SA under chilling stress. These results suggest that SA participated in grafting-induced chilling tolerance by stimulating the biosynthesis of ABA and H2O2. H2O2, as a downstream signaler of ABA, mediates SA-induced chilling tolerance in grafted cucumber plants.

Au nanoring arrays as surface enhanced Raman spectroscopy substrate for chemical component study of individual atmospheric aerosol particle.

Monolayer-ordered gold nanoring arrays were prepared by ion-sputtering method and used as surface enhanced Raman spectroscopy (SERS) substrates to test the individual atmospheric aerosols particle. Compared to other methods used for testing atmospheric aerosols particles, the collection and subsequent detection in our work is performed directly on the gold nanoring SERS substrate without any treatment of the analyte. The SERS performance can be tuned by changing the depth of the gold nanoring cavity as originating from coupling of dipolar modes at the inner and outer surfaces of the nanorings. The electric field exhibits uniform enhancement and polarization in the ordered Au nanoring substrate, which can improve the accuracy for detecting atmospheric aerosol particles. Combined with Raman mapping, the information about chemical composition of individual atmospheric aerosols particle and distribution of specific components can be presented visually. The results show the potential of SERS in enabling improved analysis of aerosol particle chemical composition, mixing state, and other related physicochemical properties.

Insight into the Formation and Transfer Process of the First Intermediate of CO2 Reduction over Ag-Decorated Dendritic Cu.

It is still poorly understood how the first intermediates of CO2 reduction are formed and converted to multi-carbon products over Cu-based electrodes. Herein, Ag is used to decorate dendritic Cu and a high Faradaic efficiency (FE) for C2 H4 (25 %) is obtained on a CuAg electrode, which is about five times higher than dendritic Cu. The intermediates including *CO2 - , OH groups, Cu-CO, C-O rotation, and CHx species are investigated by in situ Raman spectroscopy. This work provides spectroscopic evidence that the first intermediate of CO2 reduction on Ag-decorated Cu is carboxylate anion *CO2 - bonded with the catalyst surface through the C and O atom. The formation and evolution process of the *CO2 - intermediate over the applied potential are investigated in depth as well. This research contributes to a better understanding of the mechanism of CO2 reduction and multi-carbon product formation pathways over Ag-decorated Cu.

Photochemical Oxidation of Water-Soluble Organic Carbon (WSOC) on Mineral Dust and Enhanced Organic Ammonium Formation.

Water-soluble organic carbon (WSOC), which is closely related to biogenic emissions, is of great importance in the atmosphere for its ubiquitous existence and rich abundance. Levoglucosan, a typical WSOC, is usually considered to be stable and thus used as a tracer of biomass burning. However, we found that levoglucosan can be photo-oxidized on mineral dust, with formic acid, oxalic acid, glyoxylic acid, 2,3-dioxopropanoic acid, dicarbonic acid, performic acid, mesoxalaldehyde, 2-hydroxymalonaldehyde, carbonic formic anhydride, and 1,3-dioxolane-2,4-dione detected as main products. Further, we observed the heterogeneous uptake of NH3 promoted by the carboxylic acids stemming from the photocatalytic oxidation (PCO) of levoglucosan. The mineral-dust-initiated PCO of levoglucosan and enhanced heterogeneous uptake of NH3, which are highly influenced by irradiation and moisture conditions, were for the first time revealed. The reaction mechanisms and pathways were studied in detail by diffuse reflection infrared Fourier transform spectroscopy (DRIFTS), high-pressure photon ionization time-of-flight mass spectrometry (HPPI-ToF-MS) and flow reactor systems. Diverse WSOC constituents were studied as well, and the reactivity toward NH3 is related to the number of hydroxyl groups of the WSOC molecules. This work reveals a new precursor of secondary organic aerosols and provides experimental evidence of the existence of organic ammonium salts in atmospheric particles.

Surface-Enhanced Raman Spectroscopy Facilitates the Detection of Microplastics <1 µm in the Environment.

Micro- and nanoplastics are considered one of the top pollutants that threaten the environment, aquatic life, and mammalian (including human) health. Unfortunately, the development of uncomplicated but reliable analytical methods that are sensitive to individual microplastic particles, with sizes smaller than 1 µm, remains incomplete. Here, we demonstrate the detection and identification of (single) micro- and nanoplastics by using surface-enhanced Raman spectroscopy (SERS) with Klarite substrates. Klarite is an exceptional SERS substrate; it is shaped as a dense grid of inverted pyramidal cavities made of gold. Numerical simulations demonstrate that these cavities (or pits) strongly focus incident light into intense hotspots. We show that Klarite has the potential to facilitate the detection and identification of synthesized and atmospheric/aquatic microplastic (single) particles, with sizes down to 360 nm. We find enhancement factors of up to 2 orders of magnitude for polystyrene analytes. In addition, we detect and identify microplastics with sizes down to 450 nm on Klarite, with samples extracted from ambient, airborne particles. Moreover, we demonstrate Raman mapping as a fast detection technique for submicron microplastic particles. The results show that SERS with Klarite is a facile technique that has the potential to detect and systematically measure nanoplastics in the environment. This research is an important step toward detecting nanoscale plastic particles that may cause toxic effects to mammalian and aquatic life when present in high concentrations.

Cu/Ag Sphere Segment Void Array as Efficient Surface Enhanced Raman Spectroscopy Substrate for Detecting Individual Atmospheric Aerosol.

Surface enhanced Raman spectroscopy (SERS) shows great promise in studying individual atmospheric aerosol. However, the lack of efficient, stable, uniform, large-array, and low-cost SERS substrates constitutes a major roadblock. Herein, a new SERS substrate is proposed for detecting individual atmospheric aerosol particles. It is based on the sphere segment void (SSV) structure of copper and silver (Cu/Ag) alloy. The SSV structure is prepared by an electrodeposition method and presents a uniform distribution, over large 2 cm2 arrays and at low cost. The substrate offers a high SERS enhancement factor (due to Ag) combined with lasting stability (due to Cu). The SSV structure of the arrays generates a high density of SERS hotspots (1.3 × 1014/cm2), making it an excellent substrate for atmospheric aerosol detection. For stimulated sulfate aerosols, the Raman signal is greatly enhanced (>50 times), an order of magnitude more than previously reported substrates for the same purpose. For ambient particles, collected and studied on a heavy haze day, the enhanced Raman signal allows ready observation of morphology and identification of chemical components, such as nitrates and sulfates. This work provides an efficient strategy for developing SERS substrate for detecting individual atmospheric aerosol.

Klarite as a label-free SERS-based assay: a promising approach for atmospheric bioaerosol detection.

Detecting atmospheric bioaerosols in a quantitative way is highly desirable for public health and safety. This work demonstrates that surface-enhanced Raman spectroscopy (SERS) is a simple and rapid analytical technique for the detection of atmospheric bioaerosols, on a Klarite substrate. For both simulated and ambient bioaerosols, this detection assay results in an increase in the enhancement factor of the Raman signal. We report a strong SERS signal generated by bioaerosols containing living Escherichia coli deposited on Klarite. Furthermore, we demonstrate that SERS mapping can be used to estimate the percentage of airborne, living Escherichia coli. Moreover, Klarite provides differently distinct SERS spectra at different bacterial growth phases, indicating its potential to identify changes occurring in the bacterial envelope. Finally, we applied SERS for the rapid detection of Escherichia coli in ambient bioaerosols without using time-consuming and laborious culture processes. Our results represent rapid, culture-free and label-free detection of airborne bacteria in the real-world environment.

Total Synthesis of Mannopeptimycins α and ß.

The mannopeptimycins are a class of glycopeptide natural products with unusual structures and potent antibiotic activity against a range of Gram-positive multidrug-resistant bacteria. Their cyclic hexapeptide core features a pair of unprecedented ß-hydroxyenduracididines (L- and D-ßhEnd), an O-glycosylated D-Tyr carrying an α-linked dimannose, and a ß-methylated Phe residue. The D-ßhEnd unit also carries an α-linked mannopyranose at the most hindered N of its cyclic guanidine ring. Herein, we report the first total synthesis of mannopeptimycin α and ß with fully elaborated N- and O-linked sugars. Critically, a gold-catalyzed N-glycosylation of a D-ßhEnd substrate with a mannosyl ortho-alkynylbenzoate donor enabled the synthesis of the most challenging N-Man-D-ßhEnd unit with excellent efficiency and stereoselectivity. The L-ßMePhe unit was prepared using a Pd-catalyzed C-H arylation method. The L-ßhEnd, D-Tyr(di-Man), and L-ßMePhe units were prepared in gram quantities. A convergent assembly of the cyclic peptide scaffold and a single global hydrogenolysis deprotection operation provided mannopeptimycin α and ß.

Total syntheses and initial evaluation of [Ψ[C(═S)NH]Tpg4]vancomycin, [Ψ[C(═NH)NH]Tpg4]vancomycin, [Ψ[CH2NH]Tpg4]vancomycin, and their (4-chlorobiphenyl)methyl derivatives: synergistic binding pocket and peripheral modifications for the glycopeptide antibiotics.

Full details of studies are disclosed on the total syntheses of binding pocket analogues of vancomycin bearing the peripheral L-vancosaminyl-1,2-D-glucosyl disaccharide that contain changes to a key single atom in the residue-4 amide (residue-4 carbonyl O → S, NH, H2) designed to directly address the underlying molecular basis of resistance to vancomycin. Also disclosed are studies piloting the late-stage transformations conducted on the synthetically more accessible C-terminus hydroxymethyl aglycon derivatives and full details of the peripheral chlorobiphenyl functionalization of all of the binding-pocket-modified vancomycin analogues designed for dual D-Ala-D-Ala/D-Ala-D-Lac binding. Their collective assessment indicates that combined binding pocket and chlorobiphenyl peripherally modified analogues exhibit a remarkable spectrum of antimicrobial activity (VSSA, MRSA, and VanA and VanB VRE) and impressive potencies against both vancomycin-sensitive and vancomycin-resistant bacteria (MICs = 0.06-0.005 and 0.5-0.06 µg/mL for the amidine and methylene analogues, respectively) and likely benefit from two independent and synergistic mechanisms of action, only one of which is dependent on D-Ala-D-Ala/D-Ala-D-Lac binding. Such analogues are likely to display especially durable antibiotic activity that is not prone to rapidly acquired clinical resistance.

Construction of the Myrioneuron alkaloids: a total synthesis of (±)-myrioneurinol.

A strategy has been developed that culminated in a stereoselective total synthesis of the tetracyclic antimalarial Myrioneuron alkaloid myrioneurinol. The synthesis relies on three highly diastereoselective reactions, including an intramolecular chelation-controlled Michael spirocyclization of an N-Cbz-lactam titanium enolate to an α,ß-unsaturated ester for construction of the A/D-ring system and the attendant C5 (quaternary), C6 relative stereochemistry; a malonate enolate conjugate addition to a nitrosoalkene in order to install the appropriate functionality and establish the configuration at C7; and an intramolecular aza-Sakurai reaction to form the B-ring and the accompanying C9 and C10 stereocenters.

Total syntheses of the monoterpene indole alkaloids (±)-alstilobanine A and E and (±)-angustilodine.

A synthetic strategy has been developed culminating in stereoselective total syntheses of the small class of unusual monoterpenoid indole alkaloids exemplified by alstilobanines A (3) and E (2) and angustilodine (1). A pivotal step includes a novel intermolecular Michael-type addition of an indole ester dianion to a piperidine-derived nitrosoalkene to form the C15, C16 bond of the alkaloids. In addition, an application of the Romo protocol for effecting a stereoselective intramolecular nucleophile-assisted aldol-lactonization was employed, leading to a ß-lactone incorporating the requisite cis-fused 2-azadecalin moiety and also setting the C15, C19, C20 relative stereochemistry of the metabolites. It was then possible to stereoselectively effect an aldolization of a dianion derived from this indole ester ß-lactone intermediate with formaldehyde to introduce the requisite C16 hydroxymethyl group. Further manipulations of the system ultimately led to the three alkaloids in racemic form.

Reducing target binding affinity improves the therapeutic index of anti-MET antibody-drug conjugate in tumor bearing animals.

Many oncology antibody-drug conjugates (ADCs) have failed to demonstrate efficacy in clinic because of dose-limiting toxicity caused by uptake into healthy tissues. We developed an approach that harnesses ADC affinity to broaden the therapeutic index (TI) using two anti-mesenchymal-epithelial transition factor (MET) monoclonal antibodies (mAbs) with high affinity (HAV) or low affinity (LAV) conjugated to monomethyl auristatin E (MMAE). The estimated TI for LAV-ADC was at least 3 times greater than the HAV-ADC. The LAV- and HAV-ADCs showed similar levels of anti-tumor activity in the xenograft model, while the 111In-DTPA studies showed similar amounts of the ADCs in HT29 tumors. Although the LAV-ADC has ~2-fold slower blood clearance than the HAV-ADC, higher liver toxicity was observed with HAV-ADC. While the SPECT/CT 111In- and 124I- DTPA findings showed HAV-ADC has higher accumulation and rapid clearance in normal tissues, intravital microscopy (IVM) studies confirmed HAV mAb accumulates within hepatic sinusoidal endothelial cells while the LAV mAb does not. These results demonstrated that lowering the MET binding affinity provides a larger TI for MET-ADC. Decreasing the affinity of the ADC reduces the target mediated drug disposition (TMDD) to MET expressed in normal tissues while maintaining uptake/delivery to the tumor. This approach can be applied to multiple ADCs to improve the clinical outcomes.

Generative machine learning-based multi-objective process parameter optimization towards energy and quality of injection molding.

The high energy intensity and rigorous quality demand of injection molding have received significant interest under the background of the soaring production of global plastic industry. As multiple parts can be produced in a multi-cavity mold during one operation cycle, the weight differences of these parts have been demonstrated to reflect their quality performance. In this regard, this study incorporated this fact and developed a generative machine learning-based multi-objective optimization model. Such model can predict the qualification of parts produced under different processing variables and further optimize processing variables of injection molding for minimal energy consumption and weight difference amongst parts in one cycle. Statistical assessment via F1-score and R2 was performed to evaluate the performance of the algorithm. In addition, to validate the effectiveness of our model, we conducted physical experiments to measure the energy profile and weight difference under varying parameter settings. Permutation-based mean square error reduction was adopted to specify the importance of parameters affecting energy consumption and quality of injection molded parts. Optimization results indicated that the processing parameters optimization could reduce ~ 8% energy consumption and ~ 2% weight difference compared with the average operation practices. Maximum speed and first-stage speed were identified as the dominating factors affecting quality performance and energy consumption, respectively. This study could contribute to the quality assurance of injection molded parts and facilitate energy efficient and sustainable plastic manufacturing.

Impact of IgG subclass on monoclonal antibody developability.

IgG-based monoclonal antibody therapeutics, which are mainly IgG1, IgG2, and IgG4 subclasses or related variants, have dominated the biotherapeutics field for decades. Multiple laboratories have reported that the IgG subclasses possess different molecular characteristics that can affect their developability. For example, IgG1, the most popular IgG subclass for therapeutics, is known to have a characteristic degradation pathway related to its hinge fragility. However, there remains a paucity of studies that systematically evaluate the IgG subclasses on manufacturability and long-term stability. We thus conducted a systematic study of 12 mAbs derived from three sets of unrelated variable regions, each cloned into IgG1, an IgG1 variant with diminished effector functions, IgG2, and a stabilized IgG4 variant with further reduced FcγR interaction, to evaluate the impact of IgG subclass on manufacturability and high concentration stability in a common formulation buffer matrix. Our evaluation included Chinese hamster ovary cell productivity, host cell protein removal efficiency, N-linked glycan structure at the conserved N297 Fc position, solution appearance at high concentration, and aggregate growth, fragmentation, charge variant profile change, and post-translational modification upon thermal stress conditions or long-term storage at refrigerated temperature. Our results elucidated molecular attributes that are common to all IgG subclasses, as well as those that are unique to certain Fc domains, providing new insight into the effects of IgG subclass on antibody manufacturability and stability. These learnings can be used to enable a balanced decision on IgG subclass selection for therapeutic antibodies and aid in acceleration of their product development process.

CMC Regulatory Considerations for Antibody-Drug Conjugates.

Antibody-drug conjugates unite the specificity and long circulation time of an antibody with the toxicity of a chemical cytostatic or otherwise active drug using appropriate chemical linkers to reduce systemic toxicity and increase therapeutic index. This combination of a large biological molecule and a small molecule creates an increase in complexity. Multiple production processes are required to produce the native antibody, the drug and the linker, followed by conjugation of afore mentioned entities to form the final antibody-drug conjugate. The connected processes further increase the number of points of control, resulting in necessity of additional specifications and intensified analytical characterization. By combining scientific understanding of the production processes with risk-based approaches, quality can be demonstrated at those points where control is required and redundant comparability studies, specifications or product characterization are avoided. Over the product development lifecycle, this will allow process qualification to focus on those areas critical to quality and prevent redundant studies. The structure of the module 3 common technical document for an ADC needs to reflect each of the production processes and the combined overall approach to quality. Historically, regulatory authorities have provided varied expectations on its structure. This paper provides an overview of essential information to be included and shows that multiple approaches work as long as adequate cross-referencing is included.

Structure and Interaction of Ceramide-Containing Liposomes with Gold Nanoparticles as Characterized by SERS and Cryo-EM.

Due to the great potential of surface-enhanced Raman scattering (SERS) as local vibrational probe of lipid-nanostructure interaction in lipid bilayers, it is important to characterize these interactions in detail. The interpretation of SERS data of lipids in living cells requires an understanding of how the molecules interact with gold nanostructures and how intermolecular interactions influence the proximity and contact between lipids and nanoparticles. Ceramide, a sphingolipid that acts as important structural component and regulator of biological function, therefore of interest to probing, lacks a phosphocholine head group that is common to many lipids used in liposome models. SERS spectra of liposomes of a mixture of ceramide, phosphatidic acid, and phosphatidylcholine, as well as of pure ceramide and of the phospholipid mixture are reported. Distinct groups of SERS spectra represent varied contributions of the choline, sphingosine, and phosphate head groups and the structures of the acyl chains. Spectral bands related to the state of order of the membrane and moreover to the amide function of the sphingosine head groups indicate that the gold nanoparticles interact with molecules involved in different intermolecular relations. While cryogenic electron microscopy shows the formation of bilayer liposomes in all preparations, pure ceramide was found to also form supramolecular, concentric stacked and densely packed lamellar, nonliposomal structures. That the formation of such supramolecular assemblies supports the intermolecular interactions of ceramide is indicated by the SERS data. The unique spectral features that are assigned to the ceramide-containing lipid model systems here enable an identification of these molecules in biological systems and allow us to obtain information on their structure and interaction by SERS.

A Cohort Study of Surgical Indexes, Postoperative Complications, Recovery Speed, and Prognosis of Stanford Type A Aortic Dissection Compared with Traditional Sun's Operation.

Objective: The objective is to explore the surgical index, postoperative complications, recovery speed, and prognosis of Stanford type A aortic dissection (AD) compared with traditional 'Sun's operation. Methods: One hundred patients with Stanford type A AD treated from February 2018 to February 2021 were enrolled in our hospital. Patients were randomly divided into control and research group. The former group underwent traditional Sun's surgery, and the latter group underwent combined debranching surgery. The general data, surgical indexes, total amount of blood transfusion, renal function 72 hours after operation, postoperative indexes during hospitalization, and follow-up results after discharge were compared between the two groups. Results: The CPB time, ACC time, operation time, and postoperative total drainage volume of the study group were all lower than those of the control group, and the intraoperative urine volume of the study group was higher than that of the control group (P < 0.05). The total amount of RBC infused in the study group was higher than that in the control group, while the total amount of PLT, cryoprecipitate, and plasma infusion in the study group was lower than that in the control group (P < 0.05). At 72 hours after operation, BUN, Scr, and UA in the study group were significantly lower than those in the control group (P < 0.05). The number of the secondary intubation, hemodialysis, neurological complications, and deaths in the study group was significantly lower than that in the control group (P < 0.05). Conclusion: Both Sun's operation and branch removal are more effective treatment methods, and the two different surgical methods have different indications, advantages, and disadvantages, so different surgical methods can be chosen according to different conditions for Stanford AD. The possible postoperative complications should be comprehensively analyzed in the clinical work in order to reduce the occurrence of postoperative complications and improve the cure rate.

Effect of Environmental pH on Mineralization of Anaerobic Iron-Oxidizing Bacteria.

Freshwater lakes are often polluted with various heavy metals in the Anthropocene. The iron-oxidizing microorganisms and their mineralized products can coprecipitate with many heavy metals, including Al, Zn, Cu, Cd, and Cr. As such, microbial iron oxidation can exert a profound impact on environmental remediation. The environmental pH is a key determinant regulating microbial growth and mineralization and then influences the structure of the final mineralized products of anaerobic iron-oxidizing bacteria. Freshwater lakes, in general, are neutral-pH environments. Understanding the effects of varying pH on the mineralization of iron-oxidizing bacteria under neutrophilic conditions could aid in finding out the optimal pH values that promote the coprecipitation of heavy metals. Here, two typical neutrophilic Fe(II)-oxidizing bacteria, the nitrate-reducing Acidovorax sp. strain BoFeN1 and the anoxygenic phototrophic Rhodobacter ferrooxidans strain SW2, were selected for studying how their growth and mineralization response to slight changes in circumneutral pH. By employing focused ion beam/scanning electron microscopy (FIB-SEM) and transmission electron microscopy (TEM), we examined the interplay between pH changes and anaerobic iron-oxidizing bacteria and observed that pH can significantly impact the microbial mineralization process and vice versa. Further, pH-dependent changes in the structure of mineralized products of bacterial iron oxidation were observed. Our study could provide mechanical insights into how to manipulate microbial iron oxidation for facilitating remediation of heavy metals in the environment.